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Gene FLT3
Variant D835I
Impact List missense
Protein Effect unknown
Gene Variant Descriptions FLT3 D835I lies within the protein kinase domain activation loop of the Flt3 protein (PMID: 11290608). D835I has been demonstrated to promote secondary drug resistance in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 27908881), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Jun 2022).
Associated Drug Resistance Y

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Transcript NM_004119.2
gDNA chr13:g.28018504_28018505delGAinsAT
cDNA c.2503_2504delGAinsAT
Protein p.D835I
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004119.2 chr13:g.28018504_28018505delGAinsAT c.2503_2504delGAinsAT p.D835I RefSeq GRCh38/hg38
NM_004119 chr13:g.28018504_28018505delTCinsAT c.2503_2504delGAinsAT p.D835I RefSeq GRCh38/hg38

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  • Simple literal full or partial string matches
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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 exon 14 ins FLT3 D835I hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) resulted in reduced cell viability in transformed cells expressing FLT3 ITD with FLT3 D835I in culture (PMID: 32040554). 32040554
FLT3 exon 14 ins FLT3 D835I hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835I in culture (PMID: 35395091). 35395091
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 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 resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D835I were resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). 35395091
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 D835I hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835I in culture (PMID: 35395091). 35395091
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 hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835I in culture (PMID: 35395091). 35395091
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
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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 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 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 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) (PMID: 32171751; ESMO.org). 32171751 detail...
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 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 as first-line treatment for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (PMID: 32171751; ESMO.org). 32171751 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 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 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 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 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 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 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 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 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 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 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 predicted - sensitive ERAS-601 + Gilteritinib Preclinical Actionable In a preclinical study, the combination of ERAS-601 and Xospata (gilteritinib) demonstrated synergy, resulting in decreased viability of acute myeloid leukemia cells harboring FLT3 mutations in culture and inhibition of tumor growth in in vivo models (Cancer Res (2022) 82 (12_Supplement): 3345). detail...
Molecular Profile Protein Effect Treatment Approaches
FLT3 D835I unknown
FLT3 exon 14 ins FLT3 D835I
FLT3 exon 14 ins FLT3 F691L FLT3 D835I