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Gene FLT3
Variant D835Y
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions FLT3 D835Y lies within the protein kinase domain activation loop of the Flt3 protein (UniProt.org, PMID: 11290608). D835Y results in constitutive phosphorylation of Flt3 and activation of Stat5, Erk signaling, leading to transformation of cultured cells (PMID: 15256420, PMID: 30651561), and has been demonstrated to promote secondary drug resistance in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 22504184, PMID: 29187377).
Associated Drug Resistance Y

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Transcript NM_004119.2
gDNA chr13:g.28018505C>A
cDNA c.2503G>T
Protein p.D835Y
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004119.2 chr13:g.28018505C>A c.2503G>T p.D835Y RefSeq GRCh38/hg38
NM_004119 chr13:g.28018505C>A c.2503G>T p.D835Y RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 D835Y hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Quizartinib (AC220) inhibited growth of transformed hematologic cells expressing FLT3 D835Y in culture (PMID: 31309543). 31309543
FLT3 D835Y leukemia sensitive E6201 Preclinical Actionable In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines over expressing FLT3 D835Y in culture (PMID: 26822154). 26822154
FLT3 D835Y hematologic cancer sensitive SKI-G-801 Preclinical - Cell culture Actionable In a preclinical study, cells expressing FLT3 D835Y were sensitive to SKI-G-801 in culture, demonstrating inhibition of cell growth and inhibition of Flt3 autophosphorylation (PMID: 24532805). 24532805
FLT3 D835Y acute promyelocytic leukemia predicted - sensitive Arsenic trioxide + Cytarabine + Methotrexate + Tretinoin Case Reports/Case Series Actionable In a clinical case study, a patient with acute promyelocytic leukemia harboring FLT3 D835Y demonstrated a complete molecular remission after treatment with Trisenox (arsenic trioxide) and Vesanoid (tretinoin) combined with Cytosar-U (cytarabine) and Methotrexate (PMID: 27626069). 27626069
FLT3 D835Y hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib decreased cell proliferation of transformed mouse cells expressing FLT3 D835Y (PMID: 30651561). 30651561
FLT3 D835Y hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib inhibited growth of transformed hematologic cells expressing FLT3 D835Y in culture (PMID: 31309543). 31309543
FLT3 D835Y hematologic cancer sensitive Dubermatinib Preclinical - Cell culture Actionable In a preclinical study, Dubermatinib (TP-0903) inhibited growth of transformed cells expressing FLT3 D835Y in culture (PMID: 33268594). 33268594
FLT3 D835Y hematologic cancer resistant Avapritinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3 D835Y were resistant to Ayvakit (avapritinib)-induced growth inhibition in culture (PMID: 31309543). 31309543
FLT3 D835Y hematologic cancer sensitive Danusertib + Palbociclib Preclinical - Cell culture Actionable In a preclinical study, the combination of Ibrance (palbociclib) and Danusertib (PHA-739358) resulted in a synergistic effect, leading to a greater decrease in cell viability of transformed cells expressing FLT3 D835Y in culture compared to either agent alone (PMID: 30544932). 30544932
FLT3 D835Y hematologic cancer sensitive Everolimus + Palbociclib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Ibrance (palbociclib) and Afinitor (everolimus) resulted in a synergistic effect in transformed cells expressing FLT3 D835Y, demonstrating a greater reduced cell viability compared to either agent alone (PMID: 30544932). 30544932
FLT3 D835Y acute promyelocytic leukemia predicted - resistant Tretinoin Case Reports/Case Series Actionable In a clinical case study, a patient with acute promyelocytic leukemia developed meningeal relapse after maintenance therapy with Vesanoid (tretinoid), which was found to be due to a FLT3 D835Y variant (PMID: 27626069). 27626069
FLT3 D835Y Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3 D835Y were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 D835Y hematologic cancer sensitive Palbociclib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells expressing FLT3 D835Y were sensitive to treatment with Ibrance (palbociclib), demonstrating reduced cell viability in culture and tumor growth inhibition in cell line xenograft models (PMID: 30544932). 30544932
FLT3 D835Y hematologic cancer sensitive HQP1351 Preclinical - Cell culture Actionable In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3 D835Y in culture (PMID: 32247263). 32247263
FLT3 D835Y acute myeloid leukemia predicted - sensitive LAM-003 Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived acute myeloid leukemia cells harboring FLT3 D835Y demonstrated sensitivity to LAM-003 treatment in culture (PMID: 31751472). 31751472
FLT3 D835Y hematologic cancer sensitive Alisertib + Palbociclib Preclinical - Cell culture Actionable In a preclinical study, the combination treatment of Ibrance (palbociclib) and Alisertib (MLN8237) resulted in a synergistic effect in transformed cells expressing FLT3 D835Y, demonstrating a greater reduction in cell viability compared to either agent alone (PMID: 30544932). 30544932
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 D835Y in culture (Clin Cancer Res 2017; 23(24_Suppl):Abstract nr 25). detail...
FLT3 D835Y hematologic cancer resistant Sorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3 D835Y were resistant to Nexavar (sorafenib)-induced growth inhibition in culture (PMID: 31309543). 31309543
FLT3 D835Y hematologic cancer sensitive Crenolanib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib, in combination with Mekinist (trametinib), synergistically decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y (PMID: 30651561). 30651561
FLT3 D835Y hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing FLT3 D835Y in culture (PMID: 31309543). 31309543
FLT3 D835Y hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited growth of transformed hematologic cells expressing FLT3 D835Y in culture (PMID: 31309543). 31309543
FLT3 D835Y 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 FLT3 D835Y in culture (PMID: 33391463). 33391463
FLT3 D835Y Advanced Solid Tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, treatment with Rydapt (midostaurin) inhibited FLT3 phosphorylation and resulted in decreased proliferation and viability of transformed cells expressing FLT3 D835Y in culture (PMID: 12124173). 12124173
FLT3 D835Y 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 D835Y in culture (PMID: 26822154). 26822154
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 FLT3 D835Y in culture (PMID: 27158668). 27158668
FLT3 D835Y acute myeloid leukemia sensitive Palbociclib Preclinical - Cell culture Actionable In a preclinical study, patient-derived acute myeloid leukemia cells harboring FLT3 D835Y were sensitive to treatment with Ibrance (palbociclib) in culture, demonstrating reduced cell viability and colony formation (PMID: 30544932). 30544932
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 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 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 hematologic cancer sensitive Momelotinib Preclinical - Cell culture Actionable In a preclinical study, Momelotinib (CYT387) decreased phosphorylation of Flt3 and Stat5 and inhibited proliferation of transformed cells expressing FLT3-ITD and FLT3 D835Y in culture (PMID: 34768286). 34768286
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 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 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 - 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 F691L FLT3 D835Y hematologic cancer resistant Momelotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 F691L and D835Y demonstrated resistance to Momelotinib (CYT387) in culture (PMID: 34768286). 34768286
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 N676D FLT3 D835Y hematologic cancer sensitive SKI-G-801 Preclinical - Cell culture Actionable In a preclinical study, cells co-expressing FLT3 D835Y 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 F691L FLT3 D835Y hematologic cancer resistant Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib did not decrease cell proliferation of transformed mouse cells expressing Flt3 D835Y and Flt3 F691L, indicating F691L as a resistance mutation since D835Y was sensitive alone (PMID: 30651561). 30651561
FLT3 D200N FLT3 D835Y hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y and Flt3 D200N (PMID: 30651561). 30651561
FLT3 L601F FLT3 D835Y hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y and Flt3 L601F (PMID: 30651561). 30651561
FLT3 D835Y IDH1 wild-type hematologic cancer sensitive AGI-5198 + Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib, in combination with AGI-5198, synergistically decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y and Idh1 wild-type (PMID: 30651561). 30651561
FLT3 D835Y IDH1 wild-type hematologic cancer resistant AGI-5198 Preclinical - Cell culture Actionable In a preclinical study, AGI-5198, did not decrease cell proliferation of transformed mouse cells expressing Flt3 D835Y and Idh1 wild-type (PMID: 30651561). 30651561
FLT3 D835Y IDH1 wild-type hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib, decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y and Idh1 wild-type (PMID: 30651561). 30651561
FLT3 D835Y IDH1 R132H hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib, decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y and Idh1 R132H (PMID: 30651561). 30651561
FLT3 D835Y IDH1 R132H hematologic cancer sensitive AGI-5198 + Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib, in combination with AGI-5198, synergistically decreased cell proliferation of transformed mouse cells expressing Flt3 D835Y and Idh1 R132H (PMID: 30651561). 30651561
FLT3 D835Y IDH1 R132H hematologic cancer resistant AGI-5198 Preclinical - Cell culture Actionable In a preclinical study, AGI-5198, did not decrease cell proliferation of transformed mouse cells expressing Flt3 D835Y and Idh1 R132H (PMID: 30651561). 30651561
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 D835X 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), D835, or I836 mutation (FDA.gov; NCT02421939). detail... detail...
FLT3 D835X 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). detail... 28644114 detail...
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 D835X acute myeloid leukemia sensitive Crenolanib Phase I Actionable In a Phase I trial, Crenolanib treatment resulted in an overall survival (OS) of 185 days in AML patients harboring FLT3 D835X that received no prior therapy (J Clin Oncol 34, 2016 (suppl; abstr 7008)). detail...
FLT3 D835X myelodysplastic syndrome not applicable N/A Guideline Prognostic FLT3 D835 mutations are associated with poor prognosis in patients with myelodysplastic syndromes (NCCN.org). detail...
FLT3 D835X acute myeloid leukemia predicted - sensitive LAM-003 Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived acute myeloid leukemia cells harboring FLT3 D835X demonstrated sensitivity to LAM-003 treatment in culture (PMID: 31751472). 31751472
FLT3 exon20 acute myeloid leukemia sensitive Gilteritinib Guideline Actionable Xospata (gilteritinib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org). detail...
FLT3 exon20 acute myeloid leukemia sensitive Cytarabine + Daunorubicin + Midostaurin Guideline Actionable Rydapt (midostaurin), in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine), is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org). detail...
FLT3 mutant acute myeloid leukemia sensitive E6201 Preclinical Actionable In a preclinical study, acute myeloid leukemia cell lines harboring FLT3 mutations demonstrated increased sensitivity to E6201 induced growth inhibition and apoptosis in culture compared to FLT3 wild-type cells (PMID: 26822154). 26822154
FLT3 mutant acute myeloid leukemia sensitive UNC2025 Preclinical Actionable In a preclinical study, UNC2025 inhibited FLT3 activation and growth of acute myeloid leukemia cells harboring a FLT3-ITD mutation in culture (PMID: 25068800). 25068800
FLT3 mutant acute myeloid leukemia sensitive Azacitidine + Midostaurin Phase Ib/II Actionable In a Phase Ib/II trial, acute myeloid leukemia patients harboring a FLT3 mutation demonstrated an improved remission duration when treated with the combination therapy, Rydapt (midostaurin) and Vidaza (azacitidine) (PMID: 25530214). 25530214
FLT3 mutant acute myeloid leukemia sensitive Cytarabine + Daunorubicin + Midostaurin FDA approved - Has 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 (HR=0.78, p=0.009) and event-free survival (HR=0.78, p=0.002) in patients with FLT3-mutant (ITD, D835X, and I836X mutations) acute myeloid leukemia compared to Cytosar-U (cytarabine) and Daunorubicin with placebo (PMID: 28644114; NCT00651261). 28644114 detail... detail...
FLT3 mutant acute myeloid leukemia sensitive Cytarabine + Daunorubicin + Midostaurin Phase Ib/II Actionable In a Phase Ib clinical trial, Rydapt (midostaurin) treatment after Daunorubicin and Cytosar-U (cytarabine) induction resulted in complete remission in 92% (12/13) of acute myeloid leukemia patients carrying FLT3 mutations, although overall survival rate was similar to patients with wild-type FLT3 (PMID: 22627678). 22627678
FLT3 mutant acute myeloid leukemia sensitive Gilteritinib FDA approved - Has 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), D835, or I836 mutation (FDA.gov; NCT02421939). detail... detail...
FLT3 mutant acute myeloid leukemia sensitive Gilteritinib Phase Ib/II Actionable In a Phase I/II trial, treatment with Gilteritinib (ASP2215) resulted in an overall response rate of 49% (93/191) in patients with relapsed or refractory acute myeloid leukemia harboring FLT3 mutations, compared to 12% (7/58) in patients with wild-type FLT3 (PMID: 28645776; NCT02014558). detail... 28645776
FLT3 mutant acute myeloid leukemia sensitive Cytarabine + Venetoclax Phase Ib/II Actionable In a Phase I/II trial, Venclexta (venetoclax) in combination with low-dose cytarabine resulted in complete remission or complete remission with incomplete count recovery in 44% (7/16) of patients with acute myeloid leukemia harboring FLT3 mutations who were ineligible for intensive chemotherapy (ASH Annual Meeting, Dec 2018, Abstract 284; NCT02287233). detail...
FLT3 mutant acute myeloid leukemia sensitive Cytarabine + Venetoclax Guideline Actionable Venclexta (venetoclax) in combination with Cytosar-U (cytarabine) is included in guidelines for adult patients with acute myeloid leukemia harboring a FLT3 mutation (NCCN.org). detail...
FLT3 mutant acute myeloid leukemia sensitive Azacitidine + Venetoclax Guideline Actionable Venclexta (venetoclax) in combination with Vidaza (azacitidine) is included in guidelines for adult patients with acute myeloid leukemia harboring a FLT3 mutation (NCCN.org). detail...
FLT3 mutant acute myeloid leukemia sensitive Zotiraciclib Preclinical - Cell line xenograft Actionable In a preclinical study, Zotiraciclib (TG02) inhibited growth of FLT3-mutated acute myeloid leukemia cells in culture, resulted in complete tumor regression in cell line xenograft animal models (PMID: 21860433). 21860433
FLT3 mutant acute myeloid leukemia sensitive Crenolanib Phase I Actionable In a Phase I trial, Crenolanib treatment resulted in complete response (CR) in 39% (7/18), partial response (PR) in 11% (2/18), and an overall survival (OS) of 234 days in AML patients harboring FLT3 mutations (D835X, ITD, or both) that received no prior therapy, and CR in 17% (6/36), PR in 14% (5/36), and OS of 94 days in those progressed on TKIs (J Clin Oncol 34, 2016 (suppl; abstr 7008)). detail...
FLT3 mutant acute myeloid leukemia sensitive Decitabine + Venetoclax Guideline Actionable Venclexta (venetoclax) in combination with Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring a FLT3 mutation (NCCN.org). detail...
FLT3 mutant 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 act mut leukemia sensitive Pexidartinib Preclinical - Cell line xenograft Actionable In a preclinical study, PLX3397 inhibited FLT3 autophosphorylation in leukemia cells overexpressing FLT3 or harboring FLT3 activating mutations, and inhibited growth of leukemia cells harboring FLT3-ITD mutations in culture and in cell line xenograft models (ASH Annual Meeting Abstracts 2011 118: 3632). detail...
FLT3 act mut acute myeloid leukemia sensitive Palbociclib + SGI-1776 Preclinical Actionable In a preclinical study, Ibrance (palbociclib) and SGI-1776 were synergistic towards growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 act mut acute myeloid leukemia sensitive VS-5584 Preclinical - Cell line xenograft Actionable In a preclinical study, VS-5584 inhibited PI3K/mTOR signaling and cell proliferation in a FLT3-ITD positive human acute myeloid leukemia cell line in culture, and inhibited tumor growth in xenograft models (PMID: 23270925). 23270925
FLT3 act mut acute myeloid leukemia sensitive TCS 359 Preclinical Actionable In a preclinical study, TCS-359 inhibited growth of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 act mut acute myeloid leukemia sensitive Palbociclib + TCS 359 Preclinical Actionable In a preclinical study, Ibrance (palbociclib) following TCS-359 treatment enhanced growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 act mut acute myeloid leukemia sensitive Palbociclib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) blocked growth, induced apoptosis, and inhibited STAT activation in human FLT3-ITD positive human acute myeloid leukemia cells in culture (PMID: 27099147). 27099147
FLT3 act mut acute myeloid leukemia sensitive Palbociclib + Tandutinib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) and tandutinib (MLN518) were synergistic towards growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 act mut acute myeloid leukemia sensitive Crenolanib Phase II Actionable In a Phase II trial, relapsed or refractory acute myeloid leukemia patients harboring FLT3 activating mutations without a history of FLT3 therapy demonstrated a significantly greater overall survival and event free survival compared to those that had prior FLT3 therapy when treated with Crenolanib (ASH meeting, Dec 2014, abstract #389). detail...
FLT3 act mut acute myeloid leukemia sensitive Cytarabine + Daunorubicin + Sunitinib Phase Ib/II Actionable In a Phase Ib/II trial, 59% (13/22) of acute myeloid leukemia patients harboring FLT3 activating mutations achieved complete remission following treatment with Sutent (sunitinib) in combination with Cytarabine and Daunorubicin (PMID: 25818407). 25818407
FLT3 act mut acute myeloid leukemia sensitive Palbociclib + Quizartinib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) and Quizartinib (AC220) were synergistic towards growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147