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| Gene | FLT3 |
| Variant | exon 14 ins |
| Impact List | indel |
| Protein Effect | gain of function - predicted |
| Gene Variant Descriptions | FLT3 exon 14 ins refers to a series of internal tandem duplications (ITD) typically occurring in exon 14 and within the juxtamembrane domain of the Flt3 protein (PMID: 12970773). Exon 14 ins mutations often result in constitutive activation of Flt3 (PMID: 12970773) and therefore, is predicted to lead to a gain of Flt3 protein function. |
| Associated Drug Resistance |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| FLT3 exon 14 ins | myeloid leukemia | sensitive | A-419259 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed myeloid leukemia cells expressing FLT3-ITD were sensitive to treatment with A-419259, demonstrating inhibition of cell growth in culture (PMID: 31790499). | 31790499 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | CUDC-907 + Gilteritinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of CUDC-907 (fimepinostat) and Xospata (gilteritinib) synergistically inhibited cell growth, decreased Flt3 signaling, and induced apoptosis in patient-derived acute myeloid leukemia cells harboring FLT3-ITD mutations in culture, and resulted in prolonged survival compared to either agent alone in cell line xenograft models (PMID: 34099621). | 34099621 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Decitabine + Sorafenib | Guideline | Actionable | Nexavar (sorafenib) in combination with Dacogen (decitabine) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org). | detail... |
| FLT3 exon 14 ins | hematologic cancer | sensitive | LT-171-861 | Preclinical - Cell culture | Actionable | In a preclinical study, LT-171-861 inhibited cell viability and decreased FLT3 phosphorylation in transformed cells expressing a FLT3-ITD mutation in culture (PMID: 33391463). | 33391463 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Gilteritinib + LAM-003 | Preclinical - Cell culture | Actionable | In a preclinical study, LAM-003 and Xospata (gilteritinib) combination treatment reduced viability of acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). | 31751472 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | UNC1666 | Preclinical - Cell culture | Actionable | In a preclinical study, UNC1666 inhibited FLT3 phosphorylation and downstream signaling, induced apoptosis of acute myeloid leukemia cells harboring FLT3 exon 14 insertions (ITD) in culture (PMID: 25762638). | 25762638 |
| FLT3 exon 14 ins | acute myeloid leukemia | predicted - sensitive | Cytarabine + Quizartinib | Phase Ib/II | Actionable | In a Phase I/II trial, Quizartinib (AC220) in combination with Cytosar-U (cytarabine) resulted in a median overall survival of 6.7 months and a median progression-free survival of 3 months in acute myeloid leukemia patients harboring FLT3 ITD mutations (ASH 59th Annual Meeting and Exposition, Dec 2017, Abstract 723). | detail... |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | PD-0325901 + Sorafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) and PD-0325901 synergistically induced apoptosis and inhibited proliferation of acute myeloid leukemia (AML) cell lines harboring FLT3 internal tandem duplication (ITD) mutations in culture, inhibited Erk phosphorylation in FLT3-ITD mutant AML patient cells, and reduced leukemic burden in a FLT3-ITD mutant AML cell line xenograft model (PMID: 28923853). | 28923853 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Cytarabine + SKI-G-801 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of SKI-G-801 and Cytosar-U (cytarabine) resulted in a synergistic effect, demonstrating greater inhibition of proliferation compared to G-749 alone in acute myeloid leukemia cells harboring a FLT3 internal tandem duplication (PMID: 24532805). | 24532805 |
| FLT3 exon 14 ins | hematologic cancer | sensitive | Dovitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells harboring FLT3-ITD were sensitive to treatment with Dovitinib (TKI258) in culture, demonstrating decreased cell viability (PMID: 29296813). | 29296813 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | PF-04691502 + Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of PF-04691502 and Vanflyta (quizartinib) induced apoptosis and cell-cycle arrest and synergistically inhibited viability of an acute myeloid leukemia cell line harboring a FLT3-ITD mutation in culture (PMID: 34555701). | 34555701 |
| FLT3 exon 14 ins | acute myeloid leukemia | predicted - sensitive | Pacritinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Pacritinib (SB1518) induced apoptosis and inhibited proliferation of acute myeloid leukemia cells harboring a FLT3-ITD mutation in culture, and inhibited tumor growth and induced tumor regression in cell line xenograft models (PMID: 22829080). | 22829080 |
| FLT3 exon 14 ins | hematologic cancer | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). | 31309543 |
| FLT3 exon 14 ins | hematologic cancer | sensitive | GTP-14564 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing a FLT3 internal tandem duplication were sensitive to GTP-14564 treatment in culture, demonstrating decreased Stat5 activity and growth inhibition (PMID: 12815052). | 12815052 |
| FLT3 exon 14 ins | hematologic cancer | sensitive | NVP-BSK805 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD were sensitive to treatment with NVP-BSK805 in culture, demonstrating decreased cell viability (PMID: 29296813). | 29296813 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | E6201 | Preclinical - Cell culture | Actionable | In a preclinical study, E6201 induced apoptosis in blast samples derived from acute myeloid leukemia patients harboring FLT3 internal tandem duplications (ITD) in culture (PMID: 26822154). | 26822154 |
| FLT3 exon 14 ins | hematologic cancer | sensitive | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). | 31309543 |
| FLT3 exon 14 ins | acute myeloid leukemia | predicted - sensitive | APG-2575 + HQP1351 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination treatment with GZD824 (HQP1351) and APG-2575 synergistically induced apoptosis in acute myeloid leukemia cell lines harboring FLT3-ITD in culture, and led to greater tumor growth inhibition and improved survival than single agent alone in cell line xenograft models (Cancer Res 2021;81(13_Suppl):Abstract nr 1096). | detail... |
| FLT3 exon 14 ins | acute myeloid leukemia | not applicable | N/A | Guideline | Prognostic | FLT3 internal tandem duplication (FLT3-ITD) mutations are associated with inferior prognosis in acute myeloid leukemia patients with normal karyotype (NCCN.org). | detail... |
| FLT3 exon 14 ins | Advanced Solid Tumor | sensitive | Pexidartinib | Preclinical | Actionable | In a preclinical study, PLX3397 inhibited proliferation of transformed cells expressing FLT3-ITD in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Gilteritinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (ADMIRAL) that supported FDA approval, Xospata (gilteritinib) treatment resulted in complete remission (CR) or CR with partial hematologic recovery in 21% (29/138) of patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD; exon 14 insertion), D835, or I836 mutation (FDA.gov; NCT02421939). | detail... detail... |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Gilteritinib | Phase Ib/II | Actionable | In a Phase I/II trial, treatment with Gilteritinib (ASP2215) at a dose of 80mg/day or higher resulted in an overall response rate of 55% (77/141) in patients with relapsed or refractory acute myeloid leukemia harboring FLT3 internal tandem duplication mutations (PMID: 28645776; NCT02014558). | 28645776 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Gilteritinib | Guideline | Actionable | Xospata (gilteritinib) is included in the guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org). | detail... |
| FLT3 exon 14 ins | hematologic cancer | decreased response | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture with reduced potency compared to other kinase inhibitors (PMID: 31309543). | 31309543 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Sorafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, FLT3-ITD mutations correlated with sensitivity to Nexavar (sorafenib) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). | 30333627 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Sorafenib | Guideline | Actionable | Nexavar (sorafenib) is included in guidelines as maintenancy therapy for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org). | detail... |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited Flt3 phosphorylation and growth of acute myeloid leukemia cell lines harboring FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). | 31309543 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Daunorubicin + LAM-003 | Preclinical - Cell culture | Actionable | In a preclinical study, LAM-003 and Cerubidine (daunorubicin) combination treatment synergistically reduced viability of acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). | 31751472 |
| FLT3 exon 14 ins | acute myeloid leukemia | no benefit | Rebastinib | Phase I | Actionable | In a Phase I trial, acute myeloid leukemia patients harboring a FLT3 internal tandem duplication did not benefit from treatment with Rebastinib (DCC-2036) (PMID: 27927766). | 27927766 |
| FLT3 exon 14 ins | acute myeloid leukemia | predicted - sensitive | Pexidartinib | Phase Ib/II | Actionable | In a Phase I/II trial, treatment with Turalio (pexidartinib) was well-tolerated and resulted in an overall response rate of 21% (19/90) and a composite complete remission (CRc) rate of 11% (10/90) in patients with relapsed/refractory acute myeloid leukemia harboring a FLT3-ITD mutation (PMID: 32330242; NCT01349049). | 32330242 |
| FLT3 exon 14 ins | hematologic cancer | sensitive | KW-2449 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3-ITD were sensitive to treatment with KW-2449, demonstrating growth inhibition in culture (PMID: 22858906). | 22858906 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | MK2206 + Venetoclax | Preclinical - Cell culture | Actionable | In a preclinical study, MK2206 and Venclexta (venetoclax) combination treatment synergistically induced cell death of acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). | 31751472 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | LT-171-861 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, LT-171-861 inhibited cell growth, decreased FLT3 signaling, and induced apoptosis in acute myeloid leukemia cell lines and primary patient-derived peripheral blood mononuclear cells harboring FLT3-ITD mutations in culture, and resulted in tumor regression and prolonged survival in cell line xenograft models (PMID: 33391463). | 33391463 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | A-419259 | Preclinical - Cell culture | Actionable | In a preclinical study, A-419259 treatment inhibited viability of an acute myeloid leukemia cell line harboring FLT3-ITD in culture (PMID: 31790499). | 31790499 |
| FLT3 exon 14 ins | acute myeloid leukemia | predicted - sensitive | Cytarabine + Daunorubicin + Quizartinib | Phase I | Actionable | In a Phase I trial (QuANTUM-First), the combination therapy, Quizartinib (AC220) with Cytosar-U (cytarabine) and Cerubidine (daunorubicin), resulted in 67% (6/9) of acute myeloid leukemia patients harboring a FLT3-ITD achieving a composite complete response and two patients achieving morphologic leukemia-free state (PMID: 29139135; NCT01390337). | 29139135 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | ONO-7475 + Venetoclax | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, the combination of ONO-7475 and Venclexta (venetoclax) synergistically inhibited cell viability and induced apoptosis in acute myeloid leukemia cell lines harboring a FLT3-ITD mutation in culture, and reduced leukemia burden and prolonged overall survival in patient-derived xenograft (PDX) and cell line xenograft models with increased efficacy over either agent alone (PMID: 34732043). | 34732043 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | MK2206 + Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination therapy of Ibrance (palbociclib) and MK2206 resulted in a synergistic effect in acute myeloid leukemia cells expressing a FLT3-ITD, demonstrating a greater reduced cell viability compared to either agent alone (PMID: 30544932). | 30544932 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Alisertib + Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination therapy of Ibrance (palbociclib) and Alisertib (MLN8237) resulted in a synergistic effect in acute myeloid leukemia cells expressing a FLT3-ITD, demonstrating a greater reduced cell viability compared to either agent alone (PMID: 30544932). | 30544932 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | ENMD-2076 | Phase I | Actionable | In a Phase I trial, an acute myeloid leukemia patient with a FLT3-ITD mutation demonstrated anti-leukemia activity when treated with ENMD-2076 (PMID: 27406088). | 27406088 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Abivertinib + Omacetaxine mepesuccinate | Preclinical - Patient cell culture | Actionable | In a preclinical study, treatment with the combination of Abivertinib (AC0010) and Synribo (omacetaxine mepesuccinate) resulted in increased apoptosis and reduced viability of acute myeloid leukemia (AML) cell lines harboring FLT3-ITD mutations and decreased viability of patient-derived AML cells harboring FLT3-ITD mutations in culture, and reduced tumor burden and increased survival in cell line xenograft models compared to either agent alone (PMID: 31310800). | 31310800 |
| FLT3 exon 14 ins | acute myeloid leukemia | not predictive | ARQ 531 | Preclinical - Patient cell culture | Actionable | In a preclinical study, ARQ 531 treatment induced apoptosis in acute myeloid leukemia cells harboring either FLT3 exon 14 insertion (FLT3-ITD) or wild-type FLT3, and inhibited proliferation and reduced colony formation in patient cells derived from acute myeloid leukemia independent of FLT3 status in culture (PMID: 31992353). | 31992353 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Crenolanib | Phase I | Actionable | In a Phase I trial, Crenolanib treatment resulted in an overall survival (OS) of 238 days in AML patients harboring FLT3 exon 14 insertions (ITD) that received no prior therapy, and an OS of 158 days in those progressed on TKIs (J Clin Oncol 34, 2016 (suppl; abstr 7008)). | detail... |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Crenolanib | Preclinical - Patient cell culture | Actionable | In a preclinical study, FLT3-ITD mutations correlated with sensitivity to Crenolanib in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). | 30333627 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, Crenolanib inhibited Flt3 phosphorylation and growth of acute myeloid leukemia cell lines harboring FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). | 31309543 |
| FLT3 exon 14 ins | hematologic cancer | sensitive | NVP-BVB808 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD were sensitive to treatment with NVP-BVB808 in culture, demonstrating decreased cell viability (PMID: 29296813). | 29296813 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Ipatasertib + Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination therapy of Ibrance (palbociclib) and Alisertib (MLN8237) resulted in a synergistic effect in acute myeloid leukemia cells expressing a FLT3-ITD, demonstrating a greater reduced cell viability compared to either agent alone (PMID: 30544932). | 30544932 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | KX2-391 | Preclinical - Patient cell culture | Actionable | In a preclinical study, KX2-391 treatment inhibited cell viability and decreased downstream signaling in acute myeloid leukemia cell lines and patient-derived cells harboring a FLT3-ITD mutation in culture (PMID: 34217323). | 34217323 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | ASTX029 | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cell lines harboring FLT3-ITD mutations were sensitive to treatment with ASTX029 in culture (PMID: 34330842). | 34330842 |
| FLT3 exon 14 ins | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Quizartinib (AC220) inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). | 31309543 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | ARQ 531 + Venetoclax | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ARQ 531 treatment in combination with Venclexta (venetoclax) synergistically inhibited proliferation of acute myeloid leukemia cells harboring FLT3 exon 14 insertion (FLT3-ITD) in culture, and reduced tumor burden, and increased survival in a disseminated cell line xenograft model of acute myeloid leukemia compared to either agents alone (PMID: 31992353). | 31992353 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Tandutinib | Preclinical - Cell culture | Actionable | In a preclinical study, Tandutinib (CT53518) treatment inhibited viability of an acute myeloid leukemia cell line harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). | 31751472 |
| FLT3 exon 14 ins | myelodysplastic syndrome | not applicable | N/A | Guideline | Prognostic | FLT3 internal tandem duplication (FLT3-ITD) mutations are associated with poor prognosis in patients with myelodysplastic syndrome (NCCN.org). | detail... |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | MRX-2843 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, MRX-2843 inhibited Flt3 activation, resulted in growth inhibition in acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture and in cell line xenograft models, and prolonged survival in patient-derived xenograft models (PMID: 27158668). | 27158668 |
| FLT3 exon 14 ins | leukemia | predicted - sensitive | GMI-1359 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, GMI-1359 in combination with chemotherapy resulted in significant survival benefit compared to chemotherapy alone (67% vs 30%) in cell line xenograft models of FLT3-ITD leukemia (Blood 2015 126(23):3790). | detail... |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | AZD1480 + CUDC-907 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of CUDC-907 (fimepinostat) and AZD1480 inhibited phosphorylation of Stat5 and induced apoptosis in acute myeloid leukemia cell lines harboring FLT3-ITD mutations in culture, and demonstrated improved activity over either agent alone (PMID: 34099621). | 34099621 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Azacitidine + Sorafenib | Guideline | Actionable | Nexavar (sorafenib) in combination with Vidaza (azacitidine) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org). | detail... |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Selinexor + Sorafenib | Phase Ib/II | Actionable | In a Phase I/II trial, combination of Selinexor and Nexavar (sorafenib) treatment resulted in complete remission in 29% (4/14) and more than 50% blast reduction in 14% (2/14) of patients with acute myeloid leukemia harboring FLT3 ITD and/or D835 mutations (ASH, 59th Annual Meeting and Exposition, Dec 2017, Abstract 1344; NCT01607892). | detail... |
| FLT3 exon 14 ins | Advanced Solid Tumor | predicted - sensitive | Cabozantinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing a FLT3-ITD mutation were sensitive to Cometriq (cabozantinib) in culture (PMID: 21926191). | 21926191 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Cytarabine + Daunorubicin + Midostaurin | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial that supported FDA approval, treatment with Rydapt (midostaurin), combined with Cytosar-U (cytarabine) and Daunorubicin, improved overall survival (74.7 mo vs 25.6 mo) in patients with FLT3-mutant (D835X and I836X) or FLT3-ITD (exon 14 insertions) acute myeloid leukemia compared to Cytosar-U (cytarabine) and Daunorubicin with placebo (PMID: 28644114). | 28644114 detail... detail... |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Cytarabine + LAM-003 | Preclinical - Cell culture | Actionable | In a preclinical study, LAM-003 and Cytosar-U (cytarabine) combination treatment synergistically reduced viability of an acute myeloid leukemia cell line harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). | 31751472 |
| FLT3 exon 14 ins | Advanced Solid Tumor | sensitive | LAM-003 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3 internal tandem duplication (ITD) demonstrated sensitivity to LAM-003 treatment in culture (PMID: 31751472). | 31751472 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | ONO-7475 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, ONO-7475 treatment inhibited Erk phosphorylation and cell viability in acute myeloid leukemia cell lines harboring a FLT3-ITD mutation in culture, and reduced leukemia burden and prolonged survival in patient-derived xenograft (PDX) and cell line xenograft models (PMID: 34732043). | 34732043 |
| FLT3 exon 14 ins | Advanced Solid Tumor | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) demonstrated efficacy in inhibiting proliferation and viability of transformed cells expressing a FLT3-ITD mutation in culture (PMID: 12124173). | 12124173 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Dubermatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Dubermatinib (TP-0903) treatment resulted in cell cycle arrest and apoptosis, induced differentiation, and inhibited growth of acute myeloid leukemia cell lines harboring a FLT3-ITD mutation in culture, and reduced tumor growth and increased survival in cell line xenograft models (PMID: 33268594). | 33268594 |
| FLT3 exon 14 ins | B-cell acute lymphoblastic leukemia | predicted - sensitive | CD19/CD22 CAR T cells | Case Reports/Case Series | Actionable | In a clinical case study, CD19/CD22 CAR T cell treatment resulted in rapid and durable suppression of leukemia cells in a patient with refractory acute B-cell lymphoblastic leukemia harboring a FLT3 internal tandem duplication (ITD) mutation (PMID: 32005917). | 32005917 |
| FLT3 exon 14 ins | leukemia | predicted - sensitive | GMI-1359 + Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination of GMI-1359 with Nexavar (sorafenib) enhanced apoptosis compared to Nexavar (sorafenib) alone (48.9% vs 36.6%) in leukemia cell lines harboring FLT3 internal tandem duplication (ITD) mutations (Blood 2015 126(23):3790). | detail... |
| FLT3 exon 14 ins | acute myeloid leukemia | conflicting | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited Flt3 phosphorylation and growth of acute myeloid leukemia cell lines harboring FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). | 31309543 |
| FLT3 exon 14 ins | acute myeloid leukemia | conflicting | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, co-culturing human stromal cells with an acute myeloid cell line harboring a FLT3 internal tandem duplication (ITD) demonstrated resistance to Rydapt (midostaurin) treatment in culture (PMID: 31751472). | 31751472 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | LAM-003 + Venetoclax | Preclinical - Patient cell culture | Actionable | In a preclinical study, LAM-003 and Venclexta (venetoclax) combination treatment synergistically induced cell death, and inhibited viability of acute myeloid leukemia cell lines and patient-derived cells harboring FLT3 internal tandem duplication (ITD) in culture, and increased survival in a cell line xenograft model (PMID: 31751472). | 31751472 |
| FLT3 exon 14 ins | acute myeloid leukemia | predicted - sensitive | OTS167 | Preclinical - Patient cell culture | Actionable | In a preclinical study, OTS167 treatment induced cell death in patient-derived acute myeloid leukemia cells harboring FLT3-ITD in culture (PMID: 33658483). | 33658483 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | FF-10101 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, FF-10101 inhibited Flt3 autophosphorylation and cell growth of leukemic cells in culture and in AML-patient-derived xenograft models with FLT3-ITD mutations (PMID: 29187377). | 29187377 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | FF-10101 | Phase I | Actionable | In a Phase I trial, FF-10101 treatment was well tolerated, and resulted in a composite complete remission (CRc) in 13% (4/30) and a partial remission (PR) in 13% (4/30) of patients with relapsed or refractory acute myeloid leukemia, 1 of the patients achieved CRc and 2 of the patients achieved PR harbored FLT3 ITD mutations (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 7008-7008; NCT03194685). | detail... |
| FLT3 exon 14 ins | acute myeloid leukemia | predicted - sensitive | Ibrutinib | Preclinical - Cell culture | Actionable | In a preclinical study, Imbruvica (ibrutinib) treatment reduced viability of acute myeloid leukemia cells harboring FLT3-ITD mutations, however, with decreased response compared to cells treated with Abivertinib (AC0010) in culture (PMID: 31310800). | 31310800 |
| FLT3 exon 14 ins | acute myeloid leukemia | predicted - sensitive | Ibrutinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, FLT3-ITD mutations correlated with sensitivity to Imbruvica (ibrutinib) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). | 30333627 |
| FLT3 exon 14 ins | hematologic cancer | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, Crenolanib inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). | 31309543 |
| FLT3 exon 14 ins | hematologic cancer | sensitive | Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3 ITD were sensitive to treatment with Ibrance (palbociclib), demonstrating inhibition of cell growth in culture (PMID: 30544932). | 30544932 |
| FLT3 exon 14 ins | hematologic cancer | sensitive | HQP1351 | Preclinical - Cell culture | Actionable | In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD in culture (PMID: 32247263). | 32247263 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | LAM-003 + Tazemetostat | Preclinical - Cell culture | Actionable | In a preclinical study, LAM-003 and Tazemetostat (EPZ-6438) combination treatment synergistically inhibited viability of acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). | 31751472 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | A-1210477 + Venetoclax | Preclinical - Cell culture | Actionable | In a preclinical study, A-1210477 and Venclexta (venetoclax) combination treatment synergistically inhibited viability of acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). | 31751472 |
| FLT3 exon 14 ins | leukemia | sensitive | E6201 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, E6201 induced growth inhibition and apoptosis in leukemia cell lines harboring FLT3 internal tandem duplications (ITD) and reduced tumor burden in xenograft models (PMID: 26822154). | 26822154 |
| FLT3 exon 14 ins | hematologic cancer | sensitive | KX2-391 | Preclinical - Cell culture | Actionable | In a preclinical study, KX2-391 treatment inhibited cell viability, decreased downstream signaling, and induced apoptosis in cells expressing a FLT3-ITD mutation in culture (PMID: 34217323). | 34217323 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Altiratinib | Preclinical - Cell culture | Actionable | In a preclinical study, Altiratinib (DCC-0701) inhibited proliferation of an acute myeloid leukemia cell harboring a FLT3-ITD mutation in culture (PMID: 26285778). | 26285778 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | GTP-14564 | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication were sensitive to GTP-14564 treatment in culture, demonstrating growth inhibition (PMID: 12815052). | 12815052 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Sorafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) combined with Mekinist (trametinib) enhanced apoptosis in acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) mutations in culture (PMID: 28923853). | 28923853 |
| FLT3 exon 14 ins | acute myeloid leukemia | resistant | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) did not inhibit Flt3 phosphorylation or growth of acute myeloid leukemia cell lines harboring FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). | 31309543 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | CCT137690 + Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination therapy of Ibrance (palbociclib) and CCT137690 resulted in a synergistic effect in acute myeloid leukemia cells harboring a FLT3-ITD, demonstrating a greater reduced cell viability compared to either agent alone (PMID: 30544932). | 30544932 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | GSK690693 + Venetoclax | Preclinical - Cell culture | Actionable | In a preclinical study, GSK690693 and Venclexta (venetoclax) combination treatment synergistically induced cell death of acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). | 31751472 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Quizartinib | Phase I | Actionable | In a Phase I trial, acute myeloid leukemia (AML) pediatric patients harboring a FLT3-ITD mutation demonstrated a greater sensitivity to treatment with Quizartinib (AC220) when compared to AML patients with wild-type FLT3, resulting in three complete responses, four with stable disease, and a lower bone marrow blast cell count (PMID: 26920889). | 26920889 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Quizartinib (AC220) inhibited proliferation of several acute myeloid leukemia cell lines harboring different FLT3-ITD mutations in culture (PMID: 28895560). | 28895560 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Quizartinib | Phase II | Actionable | In a Phase II trial, Quizartinib (AC220) treatment resulted in a composite complete remission (CCR) in 56% (63/112; 3 complete remission (CR)) of FLT3-ITD-positive patients vs. 36% (16/44; 1 CR) of FLT3-ITD-negative patients with relapsed/refractory acute myeloid leukemia (AML) after first-line therapy, and CCR in 46% (62/136; 5 CR) of FLT3-ITD-positive vs. 30% (12/40; 1 CR) in FLT3-ITD-negative patients with relapsed/refractory AML after salvage chemotherapy or transplant (PMID: 29859851; NCT00989261). | 29859851 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Quizartinib (AC220) inhibited Flt3 phosphorylation and growth of acute myeloid leukemia cell lines harboring FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). | 31309543 |
| FLT3 exon 14 ins | acute myeloid leukemia | predicted - sensitive | Azacitidine + Quizartinib | Phase Ib/II | Actionable | In a Phase I/II trial, Quizartinib (AC220) in combination with Vidaza (azacitidine) resulted in a median overall survival of 13.4 months and a median progression-free survival of 6.9 months in acute myeloid leukemia patients harboring FLT3 ITD mutations (ASH 59th Annual Meeting and Exposition, Dec 2017, Abstract 723). | detail... |
| FLT3 exon 14 ins | acute myeloid leukemia | predicted - sensitive | IACS-13909 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, IACS-13909 decreased Erk phosphorylation in acute myeloid leukemia cells harboring FLT3 exon 14 insertion (ITD) in culture, and inhibited tumor growth and increased overall survival in cell line xenograft models (PMID: 32928921). | 32928921 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Semaxanib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication were sensitive to Semaxanib (SU5416) in culture, demonstrating inhibition of cell proliferation and inhibition of Flt3, Mapk, and Stat5 phosphorylation (PMID: 12351406). | 12351406 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | FLT3/CD3 Fabsc antibody | Preclinical - Cell culture | Actionable | In a preclinical study, treatment of an acute myeloid leukemia (AML) cell lines or patient-derived xenograft (PDX)-derived AML cells harboring a heterozygous FLT3-ITD mutation with a Fabsc FLT3/CD3 bi-specific antibody resulted in near complete eradication of AML cells in culture (PMID: 28895560). | 28895560 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | SKI-G-801 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SKI-G-801 induced apoptosis in acute myeloid leukemia cells harboring a FLT3 internal tandem duplication in culture, and inhibited tumor growth and induced tumor regression in cell line xenograft models (PMID: 24532805). | 24532805 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | LAM-003 | Preclinical - Patient cell culture | Actionable | In a preclinical study, LAM-003 treatment inhibited colony formation, and reduced viability of acute myeloid cell lines harboring FLT3 internal tandem duplication (ITD) in the presence of stromal factors that confer resistance to Xospata (gilteritinib) and Crenolanib, and induced apoptosis in patient-derived cells in culture, and induced tumor regression, and increased survival in cell line xenograft models (PMID: 31751472). | 31751472 |
| FLT3 exon 14 ins | hematologic cancer | sensitive | Dubermatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Dubermatinib (TP-0903) inhibited growth of transformed cells expressing a FLT3-ITD mutation in culture (PMID: 33268594). | 33268594 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Ponatinib | Phase I | Actionable | In a Phase I trial, Iclusig (ponatinib) resulted in a 25% (3/12) overall response rate, indicated as partial remission or better, in acute myeloid leukemia patients harboring FLT3-ITD (PMID: 23691988). | 23691988 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Ponatinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Iclusig (ponatinib) inhibited viability of patient derived acute myeloid leukemia cells harboring FLT3 ITD mutations in culture, and inhibited growth of tumors in cell line xenograft models (PMID: 21482694). | 21482694 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Entospletinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, FLT3-ITD mutations correlated with sensitivity to Entospletinib in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). | 30333627 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Entospletinib | Preclinical - Cell culture | Actionable | In a preclinical study, Entospletinib (GS-9973) treatment inhibited proliferation of acute myeloid leukemia cells harboring FLT3 exon 14 insertion (FLT3-ITD) in culture (PMID: 31992353). | 31992353 |
| FLT3 exon 14 ins | Advanced Solid Tumor | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3 internal tandem duplication (ITD) demonstrated sensitivity to Crenolanib treatment in culture (PMID: 31751472). | 31751472 |
| FLT3 exon 14 ins | acute myeloid leukemia | predicted - sensitive | SHP099 | Preclinical - Pdx | Actionable | In a preclinical study, treatment with SHP099 resulted in reduction of CD45-positive leukemic cells and decreased splenomegaly in a human primary tumor-derived xenograft model of acute myeloid leukemia harboring a FLT3-ITD mutation (PMID: 27362227). | 27362227 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Ki23819 | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication were sensitive to Ki23819 in culture, demonstrating inhibition of autophosphorylation and downstream signaling, and reduced cell proliferation (PMID: 15815726). | 15815726 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Abivertinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Abivertinib (AC0010) treatment inhibited PI3K signaling and phosphorylation of Btk, Flt3, and Stat5, induced apoptosis and cell cycle arrest, reduced viability, and inhibited colony formation in acute myeloid leukemia cell lines harboring FLT3-ITD mutations, and decreased viability of patient-derived acute myeloid leukemia blasts harboring FLT3-ITD mutations in culture (PMID: 31310800). | 31310800 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | HQP1351 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, GZD824 (HQP1351) reduced Flt3 and Stat5 phosphorylation, induced cell cycle arrest and apoptosis, and inhibited growth of acute myeloid leukemia cells harboring FLT3-ITD in culture, and suppressed tumor growth, decreased Flt3 activation, and induced apoptosis in cell line xenograft models (PMID: 32247263). | 32247263 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Gilteritinib + OTS167 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination treatment with OTS167 and Xospata (gilteritinib) synergistically inhibited cell viability and led to inhibition of colony formation in acute myeloid leukuemia (AML) cell lines harboring a FLT3-ITD and patient-derived AML cell lines with a FLT3-ITD in culture, and led to improved overall survival and reduction of leukemia burden in a cell line xenograft model (PMID: 33658483). | 33658483 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | CG-806 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, CG-806 inhibited FLT3 downstream signaling, resulted in growth inhibition of acute myeloid leukemia cells harboring FLT3 exon 14 insertion (ITD) in culture and tumor inhibition in cell line xenograft models (Clin Cancer Res 2017; 23(24_Suppl):Abstract nr 25). | detail... detail... |
| FLT3 exon 14 ins | hematologic cancer | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). | 31309543 |
| FLT3 exon 14 ins | acute myeloid leukemia | sensitive | Cytarabine + LT-171-861 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of LT-171-861 and Cytosar-U (cytarabine) synergistically inhibited cell viability in acute myeloid leukemia cell lines harboring FLT3-ITD mutations in culture (PMID: 33391463). | 33391463 |
| FLT3 exon 14 ins | leukemia | sensitive | Pexidartinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX3397 inhibited proliferation of human leukemia cells harboring FLT3-ITD in culture and in cell line xenograft models (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins | acute myeloid leukemia | predicted - sensitive | KW-2449 | Preclinical - Patient cell culture | Actionable | In a preclinical study, FLT3-ITD mutations correlated with sensitivity to KW-2449 in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). | 30333627 |
| FLT3 exon 14 ins | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing FLT3 ITD in culture (PMID: 27780853). | 27780853 |
| FLT3 exon 14 ins | leukemia | sensitive | FN-1501 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, treatment with FN-1501 reduced phoshorylation of FLT3 and downstream STAT5, ERK, and AKT, induced apoptosis and cell-cycle arrest, and decreased proliferation in a human leukemia cell line harboring a FLT3-ITD mutation in culture, and induced tumor regression in xenograft models (PMID: 29357250). | 29357250 |
| FLT3 exon 14 ins FLT3 F691L | leukemia | predicted - sensitive | CG-806 | Preclinical - Cell culture | Actionable | In a preclinical study, CG-806 inhibited FLT3 downstream signaling, resulted in growth inhibition in leukemia cells expressing FLT3 exon 14 insertion (ITD) mutation and F691L in culture (Clin Cancer Res 2017; 23(24_Suppl):Abstract nr 25). | detail... |
| FLT3 exon 14 ins FLT3 F691L | Advanced Solid Tumor | sensitive | LAM-003 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3 internal tandem duplication (ITD) and FLT3 F691L demonstrated sensitivity to LAM-003 treatment in culture (PMID: 31751472). | 31751472 |
| FLT3 exon 14 ins FLT3 F691L | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing FLT3 ITD and F691L in culture (PMID: 27780853). | 27780853 |
| FLT3 exon 14 ins FLT3 F691L | hematologic cancer | sensitive | SKI-G-801 | Preclinical - Cell culture | Actionable | In a preclinical study, cells co-expressing a FLT3 internal tandem duplication and FLT3 F691L were sensitive to SKI-G-801 in culture, demonstrating inhibition of cell growth and inhibition of Flt3 autophosphorylation (PMID: 24532805). | 24532805 |
| FLT3 exon 14 ins FLT3 F691L | hematologic cancer | sensitive | KX2-391 | Preclinical | Actionable | In a preclinical study, KX2-391 treatment inhibited viability, decreased downstream signaling, and induced apoptosis in cells expressing a FLT3-ITD mutation with FLT3 F691L in culture, and inhibited tumor growth and prolonged survival in mouse models (PMID: 34217323). | 34217323 |
| FLT3 exon 14 ins FLT3 F691L | Advanced Solid Tumor | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and F691L were resistant to Nexavar (sorafenib) in culture (PMID: 23392356). | 23392356 |
| FLT3 exon 14 ins FLT3 F691L | Advanced Solid Tumor | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and F691L were resistant to Quizartinib (AC220) in culture (PMID: 23392356). | 23392356 |
| FLT3 exon 14 ins FLT3 F691L | Advanced Solid Tumor | sensitive | Pexidartinib | Preclinical | Actionable | In a preclinical study, PLX3397 inhibited growth of transformed cells expressing a compound FLT3 F691L/FLT3-ITD mutation in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 F691L | acute myeloid leukemia | decreased response | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 F691L demonstrated a decreased response to Lestaurtinib (CEP-701) compared to treated cells harboring a FLT3 ITD and expressing FLT3 Y842C (Blood 2009 114:3776). | detail... |
| FLT3 exon 14 ins FLT3 F691L | hematologic cancer | decreased response | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing both FLT3 exon 14 insertions (ITD) and FLT3 F691L were less sensitive to Ayvakit (avapritinib)-induced growth inhibition compared to cells expressing FLT3 ITD in culture (PMID: 31309543). | 31309543 |
| FLT3 exon 14 ins FLT3 F691L | leukemia | sensitive | Pexidartinib | Preclinical | Actionable | In a preclinical study, PLX3397 inhibited proliferation of human leukemia cells harboring both FLT3-ITD and FLT3 F691L in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 F691L | hematologic cancer | decreased response | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing both FLT3 exon 14 insertions (ITD) and FLT3 F691L were less sensitive to Quizartinib (AC220)-induced growth inhibition compared to cells expressing FLT3 ITD in culture (PMID: 31309543). | 31309543 |
| FLT3 exon 14 ins FLT3 F691L | acute myeloid leukemia | sensitive | FF-10101 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, FF-10101 inhibited Flt3 autophosphorylation and growth of leukemic cell lines and inhibited growth of cell line xenografts with FLT3-ITD/F691L compound mutations (PMID: 29187377). | 29187377 |
| FLT3 exon 14 ins FLT3 F691L | hematologic cancer | sensitive | LT-171-861 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, LT-171-861 inhibited cell viability and decreased FLT3 phosphorylation in transformed cells expressing a FLT3-ITD mutation and FLT3 F691L in culture, and inhibited tumor growth and prolonged survival in cell line xenograft models (PMID: 33391463). | 33391463 |
| FLT3 exon 14 ins FLT3 F691L | hematologic cancer | resistant | KW-2449 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 F691L were resistant to treatment with KW-2449 in culture (PMID: 22858906). | 22858906 |
| FLT3 exon 14 ins FLT3 F691L | hematologic cancer | predicted - sensitive | HM43239 | Preclinical | Actionable | In a preclinical study, HM43239 treatment inhibited transformed cells expressing FLT3 ITD and F691L in cell culture (Cancer Res 2019;79(13 Suppl):Abstract nr 1293). | detail... |
| FLT3 exon 14 ins FLT3 F691L | hematologic cancer | sensitive | Dubermatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Dubermatinib (TP-0903) treatment decreased phosphorylation of Flt3 and Stat5 and inhibited growth of transformed cells expressing a FLT3-ITD mutation and FLT3 F691L in culture, and reduced peripheral blood tumor burden in cell line xenograft models (PMID: 33268594). | 33268594 |
| FLT3 exon 14 ins FLT3 F691L | hematologic cancer | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing both FLT3 exon 14 insertions (ITD) and FLT3 F691L were resistant to Nexavar (sorafenib)-induced growth inhibition in culture (PMID: 31309543). | 31309543 |
| FLT3 exon 14 ins FLT3 F691L | acute myeloid leukemia | decreased response | Lestaurtinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 F691L demonstrated a decreased response to Lestaurtinib (CEP-701) compared to treated cells harboring a FLT3 ITD and expressing FLT3 Y842C (Blood 2009 114:3776). | detail... |
| FLT3 exon 14 ins FLT3 F691L | leukemia | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines harboring FLT3 F691L in addition to FLT3 internal tandem duplications (ITD) in culture (PMID: 26822154). | 26822154 |
| FLT3 exon 14 ins FLT3 F691L | hematologic cancer | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) inhibited growth of transformed hematologic cells expressing both FLT3 exon 14 insertions (ITD) and FLT3 F691L in culture (PMID: 31309543). | 31309543 |
| FLT3 exon 14 ins FLT3 F691L | Advanced Solid Tumor | sensitive | MRX-2843 | Preclinical - Cell culture | Actionable | In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and F691L in culture (PMID: 27158668). | 27158668 |
| FLT3 exon 14 ins FLT3 F691L | acute myeloid leukemia | sensitive | MRX-2843 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant acute myeloid leukemia cells harboring FLT3 internal tandem duplication (ITD) and F691L in culture, and prolonged survival in cell line xenograft models (PMID: 27158668). | 27158668 |
| FLT3 exon 14 ins FLT3 F691L | myeloid leukemia | resistant | A-419259 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed myeloid leukemia cells co-expressing FLT-ITD and FLT3 F691L demonstrated resistance to A-419259 treatment in culture (PMID: 31790499). | 31790499 |
| FLT3 exon 14 ins FLT3 F691L | hematologic cancer | decreased response | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing both FLT3 exon 14 insertions (ITD) and FLT3 F691L were less sensitive to Crenolanib-induced growth inhibition compared to cells expressing FLT3 ITD in culture (PMID: 31309543). | 31309543 |
| FLT3 exon 14 ins FLT3 F691L | hematologic cancer | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing both FLT3 exon 14 insertions (ITD) and FLT3 F691L in culture (PMID: 31309543). | 31309543 |
| FLT3 exon 14 ins FLT3 D835Y | hematologic cancer | predicted - sensitive | HM43239 | Preclinical | Actionable | In a preclinical study, HM43239 treatment inhibited transformed cells expressing FLT3 ITD and D835Y in cell culture (Cancer Res 2019;79(13 Suppl):Abstract nr 1293). | detail... |
| FLT3 exon 14 ins FLT3 D835Y | hematologic cancer | predicted - sensitive | LT-171-861 | Preclinical - Cell culture | Actionable | In a preclinical study, LT-171-861 inhibited cell viability and decreased FLT3 phosphorylation in transformed cells expressing a FLT3-ITD mutation and FLT3 D835Y in culture (PMID: 33391463). | 33391463 |
| FLT3 exon 14 ins FLT3 D835Y | acute myeloid leukemia | predicted - resistant | Quizartinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated resistance to Vanflyta (Quizartinib) treatment in culture (PMID: 27908881). | 27908881 |
| FLT3 exon 14 ins FLT3 D835Y | hematologic cancer | no benefit | Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing FLT3 ITD and FLT3 D835Y did not respond to treatment with Ibrance (palbociclib) in culture (PMID: 30544932). | 30544932 |
| FLT3 exon 14 ins FLT3 D835Y | acute myeloid leukemia | predicted - sensitive | KX2-391 | Preclinical - Patient cell culture | Actionable | In a preclinical study, KX2-391 treatment inhibited cell viability and decreased Flt3 phosphorylation in patient-derived acute myeloid leukemia cell lines harboring a FLT3-ITD mutation with FLT3 D835Y in culture (PMID: 34217323). | 34217323 |
| FLT3 exon 14 ins FLT3 D835Y | leukemia | predicted - resistant | Pexidartinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with FLT3-ITD positive leukemia initially responded to Pexidartinib (PLX3397) therapy, but experienced relapse after emergence of FLT3 D835Y on the same allele as the FLT3-ITD mutation (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 D835Y | acute myeloid leukemia | predicted - resistant | Pexidartinib | Case Reports/Case Series | Actionable | In a Phase I/II trial, an acute myeloid leukemia patient harboring a FLT3-ITD was found to have acquired FLT3 D535Y following relapse on Turalio (pexidartinib) treatment (PMID: 34103301; NCT01349049). | 34103301 |
| FLT3 exon 14 ins FLT3 D835Y | hematologic cancer | sensitive | Dubermatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Dubermatinib (TP-0903) inhibited growth of transformed cells expressing a FLT3-ITD mutation and FLT3 D835Y in culture (PMID: 33268594). | 33268594 |
| FLT3 exon 14 ins FLT3 D835Y | acute myeloid leukemia | sensitive | MRX-2843 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant acute myeloid leukemia cells harboring FLT3 internal tandem duplication (ITD) and D835Y in culture, and prolonged survival in cell line xenograft models (PMID: 27158668). | 27158668 |
| FLT3 exon 14 ins FLT3 D835Y | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, FLT3 D835Y conferred resistance to PLX3397 when expressed in a compound mutation with FLT3-ITD in cell culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 D835Y | acute myeloid leukemia | predicted - resistant | Midostaurin | Preclinical - Patient cell culture | Actionable | In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated resistance to Rydapt (midostaurin) treatment in culture (PMID: 27908881). | 27908881 |
| FLT3 exon 14 ins FLT3 D835Y | leukemia | predicted - sensitive | CG-806 | Preclinical - Cell culture | Actionable | In a preclinical study, CG-806 inhibited FLT3 downstream signaling, resulted in growth inhibition in leukemia cells expressing FLT3 exon 14 insertion (ITD) mutation and D835Y in culture (Clin Cancer Res 2017; 23(24_Suppl):Abstract nr 25). | detail... |
| FLT3 exon 14 ins FLT3 D835Y | acute myeloid leukemia | predicted - sensitive | Gilteritinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated sensitivity to Xospata (gilteritinib) treatment in culture, resulting in reduced cell viability (PMID: 27908881). | 27908881 |
| FLT3 exon 14 ins FLT3 D835Y | acute myeloid leukemia | predicted - sensitive | Gilteritinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of acute myeloid leukemia cells harboring a FLT3-ITD mutation and FLT3 D835Y in culture, and reduced tumor growth and increased survival in cell line xenograft models (PMID: 33268594). | 33268594 |
| FLT3 exon 14 ins FLT3 D835Y | acute myeloid leukemia | sensitive | LAM-003 | Preclinical - Patient cell culture | Actionable | In a preclinical study, LAM-003 treatment inhibited viability of an acute myeloid leukemia cell line and patient-derived cells harboring FLT3 internal tandem duplication (ITD) and FLT3 D835Y in culture (PMID: 31751472). | 31751472 |
| FLT3 exon 14 ins FLT3 D835Y | myeloid leukemia | resistant | A-419259 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed myeloid leukemia cells co-expressing FLT-ITD and FLT3 D835Y demonstrated resistance to A-419259 treatment in culture (PMID: 31790499). | 31790499 |
| FLT3 exon 14 ins FLT3 D835Y | hematologic cancer | no benefit | Danusertib + Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing FLT3 ITD and FLT3 D835Y did not respond to the combination treatment of Ibrance (palbociclib) and Danusertib (PHA-739358) in culture (PMID: 30544932). | 30544932 |
| FLT3 exon 14 ins FLT3 D835Y | acute myeloid leukemia | resistant | Sorafenib | Case Reports/Case Series | Actionable | In a clinical case study, FLT3 D835Y was identified as an acquired resistance mutation in a patient with acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD) whose disease progressed on Nexavar (sorafenib) after initial response (PMID: 27908881). | 27908881 |
| FLT3 exon 14 ins FLT3 D835Y | acute myeloid leukemia | resistant | Sorafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated resistance to Nexavar (sorafenib) treatment in culture (PMID: 27908881). | 27908881 |
| FLT3 exon 14 ins FLT3 D835Y | acute myeloid leukemia | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, an acute myeloid cell line harboring FLT3 internal tandem duplication (ITD) and FLT3 D835Y did not demonstrate sensitivity to Nexavar (sorafenib) treatment in culture (PMID: 31751472). | 31751472 |
| FLT3 exon 14 ins FLT3 D835Y | hematologic cancer | predicted - sensitive | HQP1351 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D835Y demonstrated decreased proliferation in response to GZD824 (HQP1351) in culture, but were less sensitive to treatment than cells co-expressing FLT3-ITD with other FLT3 kinase domain mutations (PMID: 32247263). | 32247263 |
| FLT3 exon 14 ins FLT3 D835Y | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing FLT3 ITD and D835Y in culture (PMID: 27780853). | 27780853 |
| FLT3 exon 14 ins FLT3 D835Y | hematologic cancer | sensitive | KX2-391 | Preclinical - Cell culture | Actionable | In a preclinical study, KX2-391 treatment inhibited cell viability, decreased downstream signaling, and induced apoptosis in cells expressing a FLT3-ITD mutation with FLT3 D835Y in culture (PMID: 34217323). | 34217323 |
| FLT3 exon 14 ins FLT3 D835Y | Advanced Solid Tumor | sensitive | MRX-2843 | Preclinical - Cell culture | Actionable | In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and D835Y in culture (PMID: 27158668). | 27158668 |
| FLT3 exon 14 ins FLT3 D835Y | acute myeloid leukemia | sensitive | FF-10101 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, FF-10101 inhibited Flt3 autophosphorylation and growth of leukemic cell lines and inhibited growth of cell line xenografts with FLT3-ITD/D835Y compound mutations (PMID: 29187377). | 29187377 |
| FLT3 exon 14 ins FLT3 D835Y | acute myeloid leukemia | sensitive | Dubermatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Dubermatinib (TP-0903) treatment resulted in cell cycle arrest and apoptosis, induced differentiation, and inhibited growth of acute myeloid leukemia cells harboring a FLT3-ITD mutation and FLT3 D835Y in culture, and reduced tumor growth and increased survival in cell line xenograft models (PMID: 33268594). | 33268594 |
| FLT3 exon 14 ins FLT3 D835Y | acute myeloid leukemia | resistant | Tandutinib | Preclinical - Cell culture | Actionable | In a preclinical study, an acute myeloid cell line harboring FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated resistance to Tandutinib (CT53518) treatment in culture (PMID: 31751472). | 31751472 |
| FLT3 exon 14 ins FLT3 D835Y | acute myeloid leukemia | predicted - sensitive | Crenolanib | Preclinical - Patient cell culture | Actionable | In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated sensitivity to Crenolanib (CP-868596) treatment in culture, resulting in reduced cell viability (PMID: 27908881). | 27908881 |
| FLT3 exon 14 ins FLT3 D835V | Advanced Solid Tumor | sensitive | MRX-2843 | Preclinical - Cell culture | Actionable | In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and D835V in culture (PMID: 27158668). | 27158668 |
| FLT3 exon 14 ins FLT3 D835V | hematologic cancer | predicted - sensitive | HQP1351 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D835V demonstrated decreased proliferation in response to GZD824 (HQP1351) in culture, but were less sensitive to treatment than cells co-expressing FLT3-ITD with other FLT3 kinase domain mutations (PMID: 32247263). | 32247263 |
| FLT3 exon 14 ins FLT3 D835V | hematologic cancer | sensitive | KX2-391 | Preclinical - Cell culture | Actionable | In a preclinical study, KX2-391 treatment inhibited cell viability and decreased downstream signaling in cells expressing a FLT3-ITD mutation with FLT3 D835V in culture (PMID: 34217323). | 34217323 |
| FLT3 exon 14 ins FLT3 D835V | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D835V were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 D835F | acute myeloid leukemia | predicted - resistant | Sorafenib | Case Reports/Case Series | Actionable | In a clinical case study, FLT3 D835F was identified as an acquired resistance mutation in a patient with acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD) whose disease progressed on Nexavar (sorafenib) after initial response (PMID: 24227820). | 24227820 |
| FLT3 exon 14 ins FLT3 D835F | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D835F were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 D835F | Advanced Solid Tumor | sensitive | MRX-2843 | Preclinical - Cell culture | Actionable | In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and D835F in culture (PMID: 27158668). | 27158668 |
| FLT3 exon 14 ins FLT3 D835F | hematologic cancer | sensitive | KX2-391 | Preclinical - Cell culture | Actionable | In a preclinical study, KX2-391 treatment inhibited cell viability and decreased downstream signaling in cells expressing a FLT3-ITD mutation with FLT3 D835F in culture (PMID: 34217323). | 34217323 |
| FLT3 exon 14 ins FLT3 D835F | acute myeloid leukemia | predicted - sensitive | Crenolanib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Crenolanib inhibited growth of blasts derived from a patient with acute myeloid leukemia harboring FLT3 internal tandem duplication (ITD) and FLT3 D835F (PMID: 24227820). | 24227820 |
| FLT3 exon 14 ins FLT3 Y842H | hematologic cancer | sensitive | FF-10101 | Preclinical - Cell culture | Actionable | In a preclinical study, FF-10101, as compared to Quizartinib, inhibited Flt3 autophosphorylation and cell proliferation of transformed 32Dcl3 murine myeloid cells expressing a human FLT3-ITD/Y842H compound mutation (PMID: 29187377). | 29187377 |
| FLT3 exon 14 ins FLT3 Y842H | Advanced Solid Tumor | decreased response | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and Y842H demonstrated reduced sensitivity to Quizartinib (AC220) in culture (PMID: 23392356). | 23392356 |
| FLT3 exon 14 ins FLT3 Y842H | Advanced Solid Tumor | decreased response | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and Y842H demonstrated reduced sensitivity to Nexavar (sorafenib) in culture (PMID: 23392356). | 23392356 |
| FLT3 exon 14 ins FLT3 Y842H | Advanced Solid Tumor | sensitive | MRX-2843 | Preclinical - Cell culture | Actionable | In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and Y842H in culture (PMID: 27158668). | 27158668 |
| FLT3 exon 14 ins FLT3 Y842H | hematologic cancer | sensitive | HQP1351 | Preclinical - Cell culture | Actionable | In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD and FLT3 Y842H in culture (PMID: 32247263). | 32247263 |
| FLT3 exon 14 ins FLT3 Y842H | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 Y842H were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 Y842C | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, FLT3 Y842C conferred resistance to PLX3397 when expressed in a compound mutation with FLT3-ITD in cell culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 Y842C | acute myeloid leukemia | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated resistance to Sutent (sunitinib) in culture (Blood 2009 114:3776). | detail... |
| FLT3 exon 14 ins FLT3 Y842C | acute myeloid leukemia | resistant | AGL2043 | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated resistance to AGL2043 in culture (Blood 2009 114:3776). | detail... |
| FLT3 exon 14 ins FLT3 Y842C | acute myeloid leukemia | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated resistance to Nexavar (sorafenib) in culture (Blood 2009 114:3776). | detail... |
| FLT3 exon 14 ins FLT3 Y842C | hematologic cancer | resistant | KW-2449 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 Y842C were resistant to treatment with KW-2449 in culture (PMID: 22858906). | 22858906 |
| FLT3 exon 14 ins FLT3 Y842C | acute myeloid leukemia | sensitive | Lestaurtinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated sensitivity to Lestaurtinib (CEP-701) in culture (Blood 2009 114:3776). | detail... |
| FLT3 exon 14 ins FLT3 Y842C | leukemia | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines harboring FLT3 Y842C in addition to FLT3 internal tandem duplications (ITD) in culture (PMID: 26822154). | 26822154 |
| FLT3 exon 14 ins FLT3 Y842C | hematologic cancer | sensitive | FF-10101 | Preclinical - Cell culture | Actionable | In a preclinical study, FF-10101, as compared to Quizartinib, inhibited Flt3 autophosphorylation and cell proliferation of transformed 32Dcl3 murine myeloid cells expressing a human FLT3-ITD/Y842C compound mutation (PMID: 29187377). | 29187377 |
| FLT3 exon 14 ins FLT3 Y842C | acute myeloid leukemia | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated sensitivity to Rydapt (midostaurin) in culture (Blood 2009 114:3776). | detail... |
| FLT3 exon 14 ins FLT3 Y842C | hematologic cancer | sensitive | LT-171-861 | Preclinical - Cell culture | Actionable | In a preclinical study, LT-171-861 inhibited cell viability and decreased FLT3 phosphorylation in transformed cells expressing a FLT3-ITD mutation and FLT3 Y842C in culture (PMID: 33391463). | 33391463 |
| FLT3 exon 14 ins FLT3 Y842C | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 Y842C were resistant to treatment with Vanflyta (Quizartinib) in culture (PMID: 22858906). | 22858906 |
| FLT3 exon 14 ins FLT3 Y842C | Advanced Solid Tumor | sensitive | MRX-2843 | Preclinical - Cell culture | Actionable | In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and Y842C in culture (PMID: 27158668). | 27158668 |
| FLT3 exon 14 ins FLT3 R834Q | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 R834Q were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 F691L FLT3 R834Q | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691Q/R834Q mutation were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 D835E | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D835E were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 F691L FLT3 D835E | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3 ITD with R834Q and F691L were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 D835H | acute myeloid leukemia | sensitive | FF-10101 | Preclinical - Pdx | Actionable | In a preclinical study, FF-10101 inhibited cell growth in AML-patient-derived xenograft models with FLT3-ITD/D835H compound mutations (PMID: 29187377). | 29187377 |
| FLT3 exon 14 ins FLT3 D835H | hematologic cancer | sensitive | Dubermatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Dubermatinib (TP-0903) inhibited growth of transformed cells expressing a FLT3-ITD mutation and FLT3 D835H in culture (PMID: 33268594). | 33268594 |
| FLT3 exon 14 ins FLT3 D835H | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, FLT3 D835H conferred resistance to PLX3397 in transformed cells when expressed as a compound mutation with FLT3-ITD in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 D835H | leukemia | resistant | Pexidartinib | Clinical Study | Actionable | In a clinical study, a patient with FLT3-ITD positive leukemia initially responded to PLX3397, but experienced relapse after emergence of a FLT3 D835H mutation on the same allele as the FLT3-ITD mutation (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 F691L FLT3 D835H | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D835H mutation were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 D835N | hematologic cancer | sensitive | HQP1351 | Preclinical - Cell culture | Actionable | In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD and FLT3 D835N in culture (PMID: 32247263). | 32247263 |
| FLT3 exon 14 ins FLT3 D835N | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D835N were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 F691L FLT3 D835N | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D835N mutation were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 F691L FLT3 D839G | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD /F691L/D839G mutation were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 D839G | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, FLT3 D835G conferred resistance to PLX3397 when expressed in a compound mutation with FLT3-ITD in cell culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 D839H | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D839H were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 F691L FLT3 Y842C | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/Y842C mutation were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 F691L FLT3 Y842H | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/Y842H mutation were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 M837G FLT3 S838R FLT3 D839H | leukemia | predicted - resistant | Pexidartinib | Case Reports/Case Series | Actionable | In a clinical case study, a leukemia patient with FLT3-ITD positive leukemia initially responded to Pexidartinib (PLX3397), but experienced relapse after emergence of a compound FLT3 M837G/S838R/D839H mutation on the FLT3-ITD allele (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 D835G | hematologic cancer | sensitive | HQP1351 | Preclinical - Cell culture | Actionable | In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD and FLT3 D835G in culture (PMID: 32247263). | 32247263 |
| FLT3 exon 14 ins FLT3 D835G | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D835G were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 F691L FLT3 D835G | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D835G mutation were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 D698N | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D698N were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 D698N | Advanced Solid Tumor | resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing FLT3 ITD and FLT3 D698N were resistant to treatment with Xospata (gilteritinib) in culture (Blood (2019) 134 (Supplement_1): 2672). | detail... |
| FLT3 exon 14 ins FLT3 F691L FLT3 D698N | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D698N mutation were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 D839A | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D839A were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 F691L FLT3 D839A | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D835A mutation were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 D839N | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D839N were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 F691L FLT3 D839N | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D839N were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 G846R | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 G846R were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 F691L FLT3 G846R | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691Q/G846R mutation were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 M664I | Advanced Solid Tumor | decreased response | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 M664I displayed reduced sensitivity to PLX3397 relative to cells expressing FLT3-ITD in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 M664I FLT3 F691L | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/M664I mutation were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 N676S | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 N676S were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 N676S | myeloid leukemia | resistant | A-419259 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed myeloid leukemia cells co-expressing FLT-ITD and FLT3 N676S demonstrated resistance to A-419259 treatment in culture (PMID: 31790499). | 31790499 |
| FLT3 exon 14 ins FLT3 N676S FLT3 F691L | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/N676S mutation were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 N841K | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 N841K were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 F691L FLT3 N841K | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/N841K mutation were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 R845G | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 R845G were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 F691L FLT3 R845G | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/R845G mutation were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 Y842S | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 Y842S were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 F691L FLT3 Y842S | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/Y842S mutation were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 F691L FLT3 D835Y | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D835Y mutation were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 S652G | leukemia | predicted - resistant | Pexidartinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with FLT3-ITD positive leukemia initially responded to Pexidartinib (PLX3397), but experienced relapse after emergence of a FLT3 S652G mutation on the same allele as FLT3-ITD (PMID: 25847190). | 25847190 |
| FLT3 exon 14 ins FLT3 N676D FLT3 Y842C | leukemia | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines harboring FLT3 N676D and Y842C in addition to FLT3 internal tandem duplications (ITD) in culture (PMID: 26822154). | 26822154 |
| FLT3 exon 14 ins FLT3 D835X | acute myeloid leukemia | sensitive | Selinexor + Sorafenib | Phase Ib/II | Actionable | In a Phase I/II trial, combination of Selinexor and Nexavar (sorafenib) treatment resulted in complete remission in 29% (4/14) and more than 50% blast reduction in 14% (2/14) of patients with acute myeloid leukemia harboring FLT3 ITD and/or D835 mutations (ASH, 59th Annual Meeting and Exposition, Dec 2017, Abstract 1344; NCT01607892). | detail... |
| FLT3 exon 14 ins FLT3 D835X | acute myeloid leukemia | sensitive | Crenolanib | Phase I | Actionable | In a Phase I trial, Crenolanib treatment resulted in an overall survival (OS) of 128 days in AML patients harboring both FLT3 D835X and exon 14 insertion (ITD) that received no prior therapy, and an OS of 63 days in those progressed on TKIs (J Clin Oncol 34, 2016 (suppl; abstr 7008)). | detail... |
| FLT3 exon 14 ins FLT3 F691I | hematologic cancer | sensitive | HQP1351 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, GZD824 (HQP1351) reduced Flt3 and Stat5 phosphorylation and inhibited growth of transformed cells expressing FLT3-ITD and FLT3 F691I in culture, and suppressed tumor growth, decreased Flt3 activation, and induced apoptosis in cell line xenograft models (PMID: 32247263). | 32247263 |
| FLT3 exon 14 ins FLT3 F691I | Advanced Solid Tumor | resistant | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and F691I were resistant to Rydapt (midostaurin) in culture (PMID: 23392356). | 23392356 |
| FLT3 exon 14 ins FLT3 F691I | Advanced Solid Tumor | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and F691I were resistant to Quizartinib (AC220) in culture (PMID: 23392356). | 23392356 |
| FLT3 exon 14 ins FLT3 F691I | Advanced Solid Tumor | decreased response | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and F691I demonstrated reduced response to Sutent (sunitinib) in culture (PMID: 23392356). | 23392356 |
| FLT3 exon 14 ins FLT3 F691I | Advanced Solid Tumor | decreased response | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3 ITD and F691I demonstrated reduced sensitivity to Alunbrig (brigatinib) compared to cells expressing FLT3 ITD in culture (PMID: 27780853). | 27780853 |
| FLT3 exon 14 ins FLT3 F691I | Advanced Solid Tumor | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and F691I were resistant to Nexavar (sorafenib) in culture (PMID: 23392356). | 23392356 |
| FLT3 exon 14 ins FLT3 N676D | hematologic cancer | sensitive | SKI-G-801 | Preclinical - Cell culture | Actionable | In a preclinical study, cells co-expressing a FLT3 internal tandem duplication and FLT3 N676D were sensitive to SKI-G-801 in culture, demonstrating inhibition of cell growth and inhibition of Flt3 autophosphorylation (PMID: 24532805). | 24532805 |
| FLT3 exon 14 ins FLT3 N676D | Advanced Solid Tumor | decreased response | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and N676D demonstrated reduced sensitivity to Quizartinib (AC220) in culture (PMID: 23392356). | 23392356 |
| FLT3 exon 14 ins FLT3 N676D | Advanced Solid Tumor | resistant | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and N676D were resistant to Rydapt (midostaurin) in culture (PMID: 23392356). | 23392356 |
| FLT3 exon 14 ins FLT3 N676D | hematologic cancer | sensitive | HQP1351 | Preclinical - Cell culture | Actionable | In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD and FLT3 N676D in culture (PMID: 32247263). | 32247263 |
| FLT3 exon 14 ins FLT3 N676D | hematologic cancer | sensitive | LT-171-861 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, LT-171-861 inhibited cell viability and decreased FLT3 phosphorylation in transformed cells expressing a FLT3-ITD mutation and FLT3 N676D in culture, and inhibited tumor growth and prolonged survival in cell line xenograft models (PMID: 33391463). | 33391463 |
| FLT3 exon 14 ins FLT3 A848P | Advanced Solid Tumor | decreased response | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and A848P demonstrated reduced sensitivity to Nexavar (sorafenib) in culture (PMID: 23392356). | 23392356 |
| FLT3 exon 14 ins FLT3 A848P | Advanced Solid Tumor | decreased response | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and A848P demonstrated reduced sensitivity to Quizartinib (AC220) in culture (PMID: 23392356). | 23392356 |
| FLT3 exon 14 ins FLT3 A848P | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and A848P were resistant to Sutent (sunitinib) in culture (PMID: 23392356). | 23392356 |
| FLT3 exon 14 ins FLT3 F621L | acute myeloid leukemia | decreased response | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication (ITD) and expressing FLT3 F621L demonstrated a decreased response to Sutent (sunitinib) in culture when compared to treated cells harboring a FLT3 ITD and expressing FLT3 Y842C (Blood 2009 114:3776). | detail... |
| FLT3 exon 14 ins FLT3 F621L | acute myeloid leukemia | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication (ITD) and expressing FLT3 F621L demonstrated sensitivity to Rydapt (midostaurin) in culture (Blood 2009 114:3776). | detail... |
| FLT3 exon 14 ins FLT3 F621L | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 F621L were sensitive to treatment with Vanflyta (Quizartinib), demonstrating growth inhibition in culture (PMID: 22858906). | 22858906 |
| FLT3 exon 14 ins FLT3 F621L | acute myeloid leukemia | sensitive | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication (ITD) and expressing FLT3 F621L demonstrated sensitivity to Nexavar (sorafenib) in culture (Blood 2009 114:3776). | detail... |
| FLT3 exon 14 ins FLT3 F621L | hematologic cancer | resistant | KW-2449 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 F621L were resistant to treatment with KW-2449 in culture (PMID: 22858906). | 22858906 |
| FLT3 exon 14 ins FLT3 F621L | acute myeloid leukemia | sensitive | Lestaurtinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication (ITD) and expressing FLT3 F621L demonstrated sensitivity to Lestaurtinib (CEP-701) in culture (Blood 2009 114:3776). | detail... |
| FLT3 exon 14 ins FLT3 F621L | acute myeloid leukemia | decreased response | AGL2043 | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication (ITD) and expressing FLT3 F621L demonstrated a decreased response to AGL2043 in culture when compared to treated cells harboring a FLT3 ITD and expressing FLT3 Y842C (Blood 2009 114:3776). | detail... |
| FLT3 exon 14 ins FLT3 LOH | acute myeloid leukemia | sensitive | FLT3/CD3 Fabsc antibody + Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with the combination of Quizartinib (AC220) and an Fabsc FLT3/CD3 bi-specific antibody resulted in increased cytotoxicity over either agent alone in an acute myeloid leukemia cell line and patient-derived xenograft (PDX)-derived AML cells with a FLT3-ITD mutation and FLT3 loss of heterozygosity, leading to near complete eradication of AML cells in culture (PMID: 28895560). | 28895560 |
| FLT3 exon 14 ins FLT3 LOH | acute myeloid leukemia | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Quizartinib (AC220) inhibited proliferation of a acute myeloid leukemia cell line harboring a FLT3-ITD mutation with FLT3 loss of heterozygosity (PMID: 28895560). | 28895560 |
| FLT3 exon 14 ins FLT3 E654D | acute myeloid leukemia | predicted - sensitive | HQP1351 | Preclinical - Patient cell culture | Actionable | In a preclinical study, GZD824 (HQP1351) reduced Flt3 and Stat5 activation and inhibited growth of patient-derived acute myeloid leukemia cells harboring FLT3-ITD and FLT3 E654D in culture (PMID: 32247263). | 32247263 |
| FLT3 exon 14 ins FLT3 G697R | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and FLT3 G697R were resistant to Vanflyta (Quizartinib) in culture (PMID: 22875611). | 22875611 |
| FLT3 exon 14 ins FLT3 G697R | hematologic cancer | resistant | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and FLT3 G697R were resistant to Rydapt (midostaurin) in culture (PMID: 15374944). | 15374944 |
| FLT3 exon 14 ins FLT3 G697R | hematologic cancer | sensitive | HQP1351 | Preclinical - Cell culture | Actionable | In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD and FLT3 G697R in culture (PMID: 32247263). | 32247263 |
| FLT3 exon 14 ins FLT3 Y842R | hematologic cancer | sensitive | HQP1351 | Preclinical | Actionable | In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD and FLT3 Y842R in culture (PMID: 32247263). | 32247263 |
| FLT3 exon 14 ins FLT3 D835A | hematologic cancer | sensitive | HQP1351 | Preclinical - Cell culture | Actionable | In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD and FLT3 D835A in culture (PMID: 32247263). | 32247263 |
| FLT3 exon 14 ins FLT3 D835I | acute myeloid leukemia | predicted - resistant | Sorafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835I demonstrated resistance to Nexavar (sorafenib) treatment in culture (PMID: 27908881). | 27908881 |
| FLT3 exon 14 ins FLT3 D835I | hematologic cancer | predicted - sensitive | HQP1351 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D835I demonstrated decreased proliferation in response to GZD824 (HQP1351) in culture, but were less sensitive to treatment than cells co-expressing FLT3-ITD with other FLT3 kinase domain mutations (PMID: 32247263). | 32247263 |
| FLT3 exon 14 ins FLT3 D835I | acute myeloid leukemia | predicted - sensitive | Gilteritinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835I demonstrated sensitivity to Xospata (gilteritinib) treatment in culture, resulting in reduced cell viability and inhibition of Flt3 phosphorylation (PMID: 27908881). | 27908881 |
| FLT3 exon 14 ins FLT3 D835I | acute myeloid leukemia | predicted - resistant | Quizartinib | Case Reports/Case Series | Actionable | In a clinical case study, FLT3 D835I was identified as an acquired resistance mutation in a patient with acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD) whose disease progressed on Vanflyta (Quizartinib) after an initial response (PMID: 27908881). | 27908881 |
| FLT3 exon 14 ins FLT3 A627P | hematologic cancer | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 A627P were resistant to treatment with Nexavar (sorafenib) in culture (PMID: 22858906). | 22858906 |
| FLT3 exon 14 ins FLT3 A627P | hematologic cancer | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 A627P were resistant to treatment with Sutent (sunitinib) in culture (PMID: 22858906). | 22858906 |
| FLT3 exon 14 ins FLT3 A627P | hematologic cancer | resistant | Lestaurtinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 A627P were resistant to treatment with Lestaurtinib (CEP-701) in culture (PMID: 22858906). | 22858906 |
| FLT3 exon 14 ins FLT3 A627P | hematologic cancer | resistant | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 A627P were resistant to treatment with Rydapt (midostaurin) in culture (PMID: 22858906). | 22858906 |
| FLT3 exon 14 ins FLT3 A627P | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 A627P were resistant to treatment with Vanflyta (Quizartinib) in culture (PMID: 22858906). | 22858906 |
| FLT3 exon 14 ins FLT3 A627P | hematologic cancer | resistant | KW-2449 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 A627P were resistant to treatment with KW-2449 in culture (PMID: 22858906). | 22858906 |
| FLT3 exon 14 ins FLT3 N676T | Advanced Solid Tumor | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing FLT3 ITD and FLT3 N676T were resistant to treatment with Vanflyta (quizartinib) in culture (Blood (2019) 134 (Supplement_1): 2672). | detail... |
| FLT3 exon 14 ins FLT3 N676T | Advanced Solid Tumor | resistant | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing FLT3 ITD and FLT3 N676T were resistant to treatment with Rydapt (midostaurin) in culture (Blood (2019) 134 (Supplement_1): 2672). | detail... |
| FLT3 exon 14 ins FLT3 F691L FLT3 D835I | acute myeloid leukemia | predicted - resistant | Crenolanib | Preclinical - Patient cell culture | Actionable | In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Crenolanib (CP-868596) treatment in culture (PMID: 27908881). | 27908881 |
| FLT3 exon 14 ins FLT3 F691L FLT3 D835I | acute myeloid leukemia | predicted - resistant | Crenolanib | Case Reports/Case Series | Actionable | In a clinical case study, FLT3 F691L was identified as an acquired resistance mutation in a patient with acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835I whose disease progressed following Crenolanib (CP-868596) treatment (PMID: 27908881). | 27908881 |
| FLT3 exon 14 ins FLT3 F691L FLT3 D835I | acute myeloid leukemia | predicted - resistant | Quizartinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Vanflyta (Quizartinib) treatment in culture (PMID: 27908881). | 27908881 |
| FLT3 exon 14 ins FLT3 F691L FLT3 D835I | acute myeloid leukemia | predicted - resistant | Midostaurin | Preclinical - Patient cell culture | Actionable | In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Rydapt (midostaurin) treatment in culture (PMID: 27908881). | 27908881 |
| FLT3 exon 14 ins FLT3 F691L FLT3 D835I | acute myeloid leukemia | predicted - resistant | Gilteritinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Xospata (gilteritinib) treatment in culture (PMID: 27908881). | 27908881 |
| FLT3 exon 14 ins FLT3 F691L FLT3 D835I | acute myeloid leukemia | predicted - resistant | Sorafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Nexavar (sorafenib) treatment in culture (PMID: 27908881). | 27908881 |
| FLT3 exon 14 ins NRAS G12D | acute myeloid leukemia | predicted - resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) failed to inhibit growth of acute myeloid leukemia cells harboring a FLT3-ITD mutation and NRAS G12D in culture (PMID: 33268594). | 33268594 |
| FLT3 exon 14 ins NRAS G12D | acute myeloid leukemia | predicted - sensitive | Dubermatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Dubermatinib (TP-0903) inhibited growth of acute myeloid leukemia cells harboring a FLT3-ITD mutation and NRAS G12D in culture (PMID: 33268594). | 33268594 |
| FLT3 exon 14 ins IDH2 R140Q | acute myeloid leukemia | predicted - resistant | Sorafenib | Preclinical | Actionable | In a preclinical study, Nexavar (sorafenib) failed to inhibit growth of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). | 33268594 |
| FLT3 exon 14 ins IDH2 R140Q | acute myeloid leukemia | predicted - resistant | Quizartinib | Preclinical | Actionable | In a preclinical study, Vanflyta (Quizartinib) failed to inhibit growth of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). | 33268594 |
| FLT3 exon 14 ins IDH2 R140Q | acute myeloid leukemia | predicted - sensitive | Dubermatinib | Preclinical | Actionable | In a preclinical study, Dubermatinib (TP-0903) treatment inhibited growth and colony formation of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture, and increased survival in mouse models (PMID: 33268594). | 33268594 |
| FLT3 exon 14 ins IDH2 R140Q | acute myeloid leukemia | predicted - resistant | Midostaurin | Preclinical | Actionable | In a preclinical study, Rydapt (midostaurin) failed to inhibit growth of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). | 33268594 |
| FLT3 exon 14 ins IDH2 R140Q | acute myeloid leukemia | predicted - sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, high dosage Xospata (gilteritinib) treatment resulted in reduced viability and colony formation of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). | 33268594 |
| FLT3 exon 14 ins IDH2 R140Q | acute myeloid leukemia | predicted - sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, high dosage Crenolanib (CP-868596) treatment resulted in reduced viability of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). | 33268594 |
| FLT3 exon 14 ins JAK1 V658F | hematologic cancer | sensitive | Midostaurin + Ruxolitinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Rydapt (midostaurin) and Jakafi (ruxolitinib) inhibited Flt3 and Stat5 phosphorylation and growth of transformed hematologic cells expressing a FLT3-ITD mutation and JAK1 V658F in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK1 V658F | hematologic cancer | sensitive | Ruxolitinib + Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Nexavar (sorafenib) and Jakafi (ruxolitinib) inhibited growth of transformed hematologic cells expressing a FLT3-ITD mutation and JAK1 V658F in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK1 V658F | hematologic cancer | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK1 V658F were resistant to treatment with Nexavar (sorafenib) in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK1 V658F | hematologic cancer | resistant | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK1 V658F were resistant to treatment with Rydapt (midostaurin) in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK1 V658F | hematologic cancer | resistant | Ruxolitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK1 V658F were resistant to treatment with Jakafi (ruxolitinib) in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK1 S703I | hematologic cancer | resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK1 S703I were resistant to treatment with Xospata (gilteritinib) in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK1 S703I | hematologic cancer | sensitive | Midostaurin + Ruxolitinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Rydapt (midostaurin) and Jakafi (ruxolitinib) inhibited downstream signaling and cell growth in transformed hematologic cells expressing a FLT3-ITD mutation and JAK1 S703I in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK1 S703I | hematologic cancer | sensitive | Midostaurin + Tofacitinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Rydapt (midostaurin) and Xeljanz (tofacitinib) inhibited growth of transformed hematologic cells expressing a FLT3-ITD mutation and JAK1 S703I in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK1 S703I | hematologic cancer | resistant | Ruxolitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK1 S703I were resistant to treatment with Jakafi (ruxolitinib) in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK1 S703I | hematologic cancer | decreased response | Pacritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Pacritinib (SB1518) treatment decreased cell proliferation and Akt and Erk phosphorylation, but did not fully inhibit Stat5 phosphorylation in transformed hematologic cells expressing a FLT3-ITD mutation and JAK1 S703I and was less effective compared to treatment with the combination of a FLT3 inhibitor and a JAK inhibitor in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK1 S703I | acute myeloid leukemia | resistant | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK1 S703I were resistant to treatment with Rydapt (midostaurin) in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK1 S703I | hematologic cancer | sensitive | Gilteritinib + Ruxolitinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Xospata (gilteritinib) and Jakafi (ruxolitinib) inhibited growth of transformed hematologic cells expressing a FLT3-ITD mutation and JAK1 S703I in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK1 S703I | hematologic cancer | resistant | Tofacitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK1 S703I were resistant to treatment with Xeljanz (tofacitinib) in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK2 V617F | hematologic cancer | resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK2 V617F were resistant to treatment with Xospata (gilteritinib) in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK2 V617F | hematologic cancer | resistant | Tofacitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK2 V617F were resistant to treatment with Xeljanz (tofacitinib) in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK2 V617F | hematologic cancer | sensitive | Midostaurin + Ruxolitinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Rydapt (midostaurin) and Jakafi (ruxolitinib) inhibited downstream signaling and cell growth in transformed hematologic cells expressing a FLT3-ITD mutation and JAK2 V617F in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK2 V617F | hematologic cancer | resistant | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK2 V617F were resistant to treatment with Rydapt (midostaurin) in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK2 V617F | hematologic cancer | resistant | Ruxolitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK2 V617F were resistant to treatment with Jakafi (ruxolitinib) in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK2 V617F | hematologic cancer | predicted - sensitive | Pacritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Pacritinib (SB1518) treatment decreased cell proliferation and downstream signaling in transformed hematologic cells expressing a FLT3-ITD mutation and JAK2 V617F in culture but may not be capable of fully inhibiting Flt3 and Jak signaling at clinically achievable concentrations (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK2 V617F | hematologic cancer | decreased response | Midostaurin + Tofacitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK2 V617F demonstrated a decreased response to treatment with the combination of Rydapt (midostaurin) and Xeljanz (tofacitinib) compared to cells expressing a FLT3-ITD mutation and activating mutations of JAK1 or JAK3 in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK2 V617F | hematologic cancer | sensitive | Gilteritinib + Ruxolitinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Xospata (gilteritinib) and Jakafi (ruxolitinib) inhibited growth of transformed hematologic cells expressing a FLT3-ITD mutation and JAK2 V617F in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK1 R724H JAK3 A573V | hematologic cancer | resistant | Ruxolitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation, JAK1 R724H, and JAK3 A573V were resistant to treatment with Jakafi (ruxolitinib) in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK1 R724H JAK3 A573V | hematologic cancer | sensitive | Midostaurin + Ruxolitinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Rydapt (midostaurin) and Jakafi (ruxolitinib) inhibited downstream signaling and cell growth in transformed hematologic cells expressing a FLT3-ITD mutation, JAK1 R724H, and JAK3 A573V in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK1 R724H JAK3 A573V | hematologic cancer | resistant | Tofacitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation, JAK1 R724H, and JAK3 A573V were resistant to treatment with Xeljanz (tofacitinib) in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK1 R724H JAK3 A573V | hematologic cancer | sensitive | Midostaurin + Tofacitinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Rydapt (midostaurin) and Xeljanz (tofacitinib) inhibited growth of transformed hematologic cells expressing a FLT3-ITD mutation, JAK1 R724H, and JAK3 A573V in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK1 R724H JAK3 A573V | acute myeloid leukemia | resistant | Midostaurin | Case Reports/Case Series | Actionable | In a clinical case study, a patient with acute myeloid leukemia harboring a FLT3-ITD mutation, JAK1 R724H, and JAK3 A573V demonstrated increased allele frequencies for JAK1 R724H (13.5% vs 22%) and JAK3 A573V (13.1% vs 23.1%) after not responding to treatment with Rydapt (midostaurin) and chemotherapy, and in a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation, JAK1 R724H, and JAK3 A573V were resistant to treatment with Rydapt (midostaurin) in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK3 V722I | hematologic cancer | resistant | Ruxolitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I were resistant to treatment with Jakafi (ruxolitinib) in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK3 V722I | hematologic cancer | decreased response | Pacritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Pacritinib (SB1518) treatment decreased cell proliferation and Akt and Erk phosphorylation, but did not fully inhibit Stat5 phosphorylation in transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I and was less effective compared to treatment with the combination of a FLT3 inhibitor and a JAK inhibitor in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK3 V722I | hematologic cancer | sensitive | Gilteritinib + Ruxolitinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Xospata (gilteritinib) and Jakafi (ruxolitinib) inhibited growth of transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK3 V722I | hematologic cancer | sensitive | Midostaurin + Tofacitinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Rydapt (midostaurin) and Xeljanz (tofacitinib) inhibited cell growth and downstream signaling of transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK3 V722I | hematologic cancer | resistant | Tofacitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I were resistant to treatment with Xeljanz (tofacitinib) in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK3 V722I | hematologic cancer | resistant | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I were resistant to treatment with Rydapt (midostaurin) in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK3 V722I | hematologic cancer | sensitive | Midostaurin + Ruxolitinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Rydapt (midostaurin) and Jakafi (ruxolitinib) inhibited downstream signaling and cell growth in transformed hematologic cells expressing aa FLT3-ITD mutation and JAK3 V722I in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK3 V722I | acute myeloid leukemia | predicted - resistant | Sorafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with acute myeloid leukemia harboring a FLT3-ITD mutation treated with Nexavar (sorafenib) was found to have acquired a JAK3 V722I mutation with a variant allele frequency of 49% upon relapse (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK3 V722I | hematologic cancer | resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I were resistant to treatment with Xospata (gilteritinib) in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK3 R953* | hematologic cancer | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 R953* in culture (PMID: 33149267). | 33149267 |
| FLT3 exon 14 ins JAK3 R953* | acute myeloid leukemia | predicted - resistant | Quizartinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with acute myeloid leukemia harboring a FLT3-ITD mutation treated with Vanflyta (quizartinib) was found to have acquired a JAK3 R953* mutation upon relapse (PMID: 33149267). | 33149267 |
| KMT2A - AFF1 FLT3 exon 14 ins | acute myeloid leukemia | predicted - sensitive | CYC065 | Preclinical - Cell culture | Actionable | In a preclinical study, an acute myeloid leukemia cell line harboring KMT2A-AFF1 and a FLT3-ITD was sensitive to treatment with CYC065 (Fadraciclib) in culture, demonstrating decreased cell viability (PMID: 32645016). | 32645016 |
| KMT2A - MLLT3 FLT3 exon 14 ins | acute myeloid leukemia | sensitive | CYC065 | Preclinical - Cell culture | Actionable | In a preclinical study, an acute myeloid leukemia cell line harboring a FLT3-ITD and KMT2A-MLLT3 was sensitive to treatment with CYC065 (Fadraciclib) in culture, demonstrating reduced cell viability, increased PARP cleavage, and decreased Mcl1 protein levels (PMID: 32645016). | 32645016 |
| FLT3 exon 14 ins FLT3 A627T | hematologic cancer | predicted - resistant | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing a FLT3-ITD mutation with FLT3 A627T demonstrated moderate resistance to treatment with Rydapt (midostaurin) in culture (PMID: 15374944). | 15374944 |
| FLT3 exon 14 ins FLT3 A627T | hematologic cancer | predicted - resistant | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing a FLT3-ITD mutation with FLT3 A627T demonstrated resistance to Rydapt (midostaurin) in culture (PMID: 17620426). | 17620426 |
| FLT3 exon 14 ins FLT3 N701K | hematologic cancer | resistant | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 N701K demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33780043). | 33780043 |
| FLT3 exon 14 ins FLT3 N676K | acute myeloid leukemia | predicted - resistant | Midostaurin | Case Reports/Case Series | Actionable | In a clinical case study, a patient with acute myeloid leukemia harboring a FLT3-ITD mutation progressed on Rydapt (midostaurin) after 288 days and was found to have acquired a FLT3 N676K mutation, and resistance was also confirmed in patient-derived cells in culture (PMID: 16150941). | 16150941 |
| FLT3 exon 14 ins FLT3 N676K | acute myeloid leukemia | predicted - resistant | Pexidartinib | Case Reports/Case Series | Actionable | In a Phase I/II trial, an acute myeloid leukemia patient harboring a FLT3-ITD was found to have acquired FLT3 N676K following relapse on Turalio (pexidartinib) treatment (PMID: 34103301; NCT01349049). | 34103301 |
| FLT3 exon 14 ins FLT3 C695S | hematologic cancer | predicted - resistant | FF-10101 | Preclinical - Cell culture | Actionable | In a preclinical study, expression of FLT3 C695S in the context of a FLT3-ITD mutation conferred resistance to inhibition of Flt3 phosphorylation by FF-10101 in transformed human cells in culture (PMID: 29187377). | 29187377 |