FLT3 D835del
Gene Variant Detail

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Gene FLT3
Variant D835del
Impact List deletion
Protein Effect gain of function
Gene Variant Descriptions FLT3 D835del results in the deletion of an amino acid from the activation loop in the protein kinase domain of the Flt3 protein at amino acid 835 (PMID: 25837374). D835del results in constitutive phosphorylation of Flt3 and activation of Stat5, Erk signaling, leading to transformation of cultured cells (PMID: 15256420).
Associated Drug Resistance
Category Variants Paths

FLT3 mutant FLT3 act mut FLT3 D835del

FLT3 mutant FLT3 exon20 FLT3 D835del

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Transcript NM_004119.3
gDNA chr13:g.28018503_28018505delATC
cDNA c.2503_2505delGAT
Protein p.D835delD
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004119.3 chr13:g.28018503_28018505delATC c.2503_2505delGAT p.D835delD RefSeq GRCh38/hg38
XM_017020486 chr13:g.28015189_28015191delTTT c.2504_2506delAAA p.K835delK RefSeq GRCh38/hg38
XM_017020486.1 chr13:g.28015189_28015191delTTT c.2504_2506delAAA p.K835delK RefSeq GRCh38/hg38
XM_011535015 chr13:g.28015681_28015683delCCA c.2503_2505delTGG p.W835delW RefSeq GRCh38/hg38
XM_011535015.3 chr13:g.28015681_28015683delCCA c.2503_2505delTGG p.W835delW RefSeq GRCh38/hg38
NM_004119.2 chr13:g.28018503_28018505delATC c.2503_2505delGAT p.D835delD RefSeq GRCh38/hg38
NM_004119 chr13:g.28018503_28018505delATC c.2503_2505delGAT p.D835delD RefSeq GRCh38/hg38
XM_011535015.2 chr13:g.28015681_28015683delCCA c.2503_2505delTGG p.W835delW RefSeq GRCh38/hg38
XM_017020486.2 chr13:g.28015189_28015191delTTT c.2504_2506delAAA p.K835delK RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 D835del 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 (D835 and I836) or FLT3-ITD (exon 14 insertions) acute myeloid leukemia compared to Cytosar-U (cytarabine) and Daunorubicin with placebo (PMID: 28644114). detail... 28644114 detail...
FLT3 D835del acute myeloid leukemia sensitive Gilteritinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (ADMIRAL) that supported FDA approval, Xospata (gilteritinib) improved median overall survival (9.3 vs 5.6 mo, HR. 0.64, p<0.001) compared to chemotherapy, resulted in superior median event-free survival (2.8 vs 0.7 mo, HR 0.79) and rate of complete remission with full or partial hematologic recovery (34.0% vs 15.3%) in patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD), D835, or I836 mutation (PMID: 31665578; NCT02421939). 31665578 detail... detail...
FLT3 D835del hematologic cancer sensitive Gilteritinib Preclinical Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited Flt3 signaling and viability in a cell line expressing FLT3 D835del in culture and inhibited growth in a transplant model (PMID: 40196870). 40196870
FLT3 D835del hematologic cancer decreased response Quizartinib Preclinical Actionable In a preclinical study, cells expressing FLT3 D835del were less sensitive to Vanflyta (quizartinib) compared to cells expressing a FLT3-ITD in culture and in a transplant model (PMID: 40196870). 40196870
FLT3 D835del hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment decreased viability in a cell line expressing FLT3 D835del in culture (PMID: 40196870). 40196870