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FLT3 I836del - Gene Variant Detail

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Gene FLT3
Variant I836del
Impact List deletion
Protein Effect gain of function
Gene Variant Descriptions FLT3 I836del results in the deletion of an amino acid in the protein kinase domain activation loop of the Flt3 protein at amino acid 836 (PMID: 12663439). I836del 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 I836del

FLT3 mutant FLT3 exon20 FLT3 I836del

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Transcript NM_004119.3
gDNA chr13:g.28018500_28018502delGAT
cDNA c.2508_2510delCAT
Protein p.I836delI
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004119.2 chr13:g.28018500_28018502delGAT c.2508_2510delCAT p.I836delI RefSeq GRCh38/hg38
XM_017020486.1 chr13:g.28015186_28015188delCAT c.2506_2508delATG p.M836delM RefSeq GRCh38/hg38
XM_011535015.2 chr13:g.28015679_28015681delATC c.2506_2508delATG p.M836delM RefSeq GRCh38/hg38
XM_011535015.3 chr13:g.28015679_28015681delATC c.2506_2508delATG p.M836delM RefSeq GRCh38/hg38
XM_011535015 chr13:g.28015679_28015681delATC c.2506_2508delATG p.M836delM RefSeq GRCh38/hg38
XM_017020486 chr13:g.28015186_28015188delCAT c.2506_2508delATG p.M836delM RefSeq GRCh38/hg38
NM_004119.3 chr13:g.28018500_28018502delGAT c.2508_2510delCAT p.I836delI RefSeq GRCh38/hg38
XM_017020486.2 chr13:g.28015186_28015188delCAT c.2506_2508delATG p.M836delM RefSeq GRCh38/hg38
NM_004119 chr13:g.28018500_28018502delGAT c.2508_2510delCAT p.I836delI RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 I836del cancer sensitive Tandutinib Preclinical - Cell culture Actionable In a preclinical study, Tandutinib (CT53518) inhibited phosphorylation of FLT3 and activation of ERK and STAT5, and reduced growth of transformed cells expressing FLT3 I836del in culture (PMID: 15256420). 15256420
FLT3 I836del cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited phosphorylation of FLT3, ERK, and STAT5, and growth of transformed cells expressing FLT3 I836del in culture (PMID: 17827387). 17827387
FLT3 I836del acute myeloid leukemia predicted - sensitive Cytarabine + Mitoxantrone + Sorafenib Case Reports/Case Series Actionable In a clinical study, combination treatment with Cytosar-U (cytarabine), Novantrone (mitoxantrone), and Nexavar (sorafenib) treatment in an acute myeloid leukemia patient harboring FLT3 I836del led to remission with negative minimal residual disease (PMID: 33563661; NCT02670525). 33563661
FLT3 I836del acute myeloid leukemia predicted - sensitive Azacitidine + Sorafenib + Venetoclax Case Reports/Case Series Actionable In a clinical study, combination treatment with Vidaza (azacitidine), Nexavar (sorafenib) and Venclexta (venetoclax) resulted in continued remission from Cytosar-U (cytarabine), Novantrone (mitoxantrone), and Nexavar (sorafenib) treatment in an acute myeloid leukemia patient harboring FLT3 I836del (PMID: 33563661; NCT02670525). 33563661
FLT3 I836del hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) resulted in reduced cell viability in transformed cells expressing FLT3 I836del in culture (PMID: 32040554). 32040554
FLT3 I836del 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). 28644114 detail... detail...
FLT3 I836del 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). detail... 31665578 detail...