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Gene | FLT3 |
Variant | D835X |
Impact List | missense |
Protein Effect | unknown |
Gene Variant Descriptions | FLT3 D835X indicates any Flt3 missense mutation that results in the replacement of the aspartic acid (D) at amino acid 835 by a different amino acid. FLT3 codon 835 mutations are hotspot mutations that often result in constitutive phosphorylation of Flt3 and activation of downstream signaling (PMID: 11290608, PMID: 15256420). |
Associated Drug Resistance |
Transcript | NM_004119.2 |
gDNA | chr13:g.28018503_28018505 |
cDNA | c.2503_2505 |
Protein | p.D835 |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004119 | chr13:g.28018503_28018505 | c.2503_2505 | p.D835 | RefSeq | GRCh38/hg38 |
NM_004119.2 | chr13:g.28018503_28018505 | c.2503_2505 | p.D835 | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
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 | 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 | 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 | 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 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 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 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... |
Molecular Profile | Protein Effect | Treatment Approaches |
---|---|---|
FLT3 D835X | unknown | FLT3 Inhibitor |
FLT3 exon 14 ins FLT3 D835X |