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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, Dec 2023). |
Associated Drug Resistance | Y |
Category Variants Paths |
FLT3 mutant FLT3 exon20 FLT3 D835X FLT3 D835I |
Transcript | NM_004119.3 |
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 | chr13:g.28018504_28018505delTCinsAT | c.2503_2504delGAinsAT | p.D835I | RefSeq | GRCh38/hg38 |
NM_004119.2 | chr13:g.28018504_28018505delGAinsAT | c.2503_2504delGAinsAT | p.D835I | RefSeq | GRCh38/hg38 |
NM_004119.3 | chr13:g.28018504_28018505delGAinsAT | c.2503_2504delGAinsAT | p.D835I | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
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 | 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 | 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 | 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 | 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 | 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 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 | hematologic cancer | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) 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 | 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 | 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 | 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 |
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 | 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 |