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Gene | FLT3 |
Variant | D835Y |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | FLT3 D835Y lies within the protein kinase domain activation loop of the Flt3 protein (UniProt.org, PMID: 11290608). D835Y results in constitutive phosphorylation of Flt3 and activation of Stat5, Erk signaling, leading to transformation of cultured cells (PMID: 15256420, PMID: 30651561), and has been demonstrated to promote secondary drug resistance in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 22504184, PMID: 29187377). |
Associated Drug Resistance | Y |
Category Variants Paths |
FLT3 mutant FLT3 act mut FLT3 D835Y FLT3 mutant FLT3 exon20 FLT3 D835X FLT3 D835Y |
Transcript | NM_004119.3 |
gDNA | chr13:g.28018505C>A |
cDNA | c.2503G>T |
Protein | p.D835Y |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004119 | chr13:g.28018505C>A | c.2503G>T | p.D835Y | RefSeq | GRCh38/hg38 |
NM_004119.2 | chr13:g.28018505C>A | c.2503G>T | p.D835Y | RefSeq | GRCh38/hg38 |
NM_004119.3 | chr13:g.28018505C>A | c.2503G>T | p.D835Y | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FLT3 D835Y | hematologic cancer | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, Crenolanib (CP-868596) decreased proliferation of transformed cells expressing FLT3 D835Y in culture (PMID: 30651561). | 30651561 |
FLT3 D835Y | hematologic cancer | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, Crenolanib inhibited growth of transformed hematologic cells expressing FLT3 D835Y in culture (PMID: 31309543). | 31309543 |
FLT3 D835Y | hematologic cancer | sensitive | Foretinib | Preclinical - Cell culture | Actionable | In a preclinical study, Foretinib (GSK1363089) inhibited viability of cultured cells expressing FLT3 D835Y (PMID: 38231480). | 38231480 |
FLT3 D835Y | hematologic cancer | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited growth of cells expressing FLT3 D835Y in culture (PMID: 38049555). | 38049555 |
FLT3 D835Y | hematologic cancer | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing FLT3 D835Y in culture (PMID: 31309543). | 31309543 |
FLT3 D835Y | Advanced Solid Tumor | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with Rydapt (midostaurin) inhibited FLT3 phosphorylation and resulted in decreased proliferation and viability of transformed cells expressing FLT3 D835Y in culture (PMID: 12124173). | 12124173 |
FLT3 D835Y | hematologic cancer | sensitive | Palbociclib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells expressing FLT3 D835Y were sensitive to treatment with Ibrance (palbociclib), demonstrating reduced cell viability in culture and tumor growth inhibition in cell line xenograft models (PMID: 30544932). | 30544932 |
FLT3 D835Y | acute myeloid leukemia | sensitive | Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, patient-derived acute myeloid leukemia cells harboring FLT3 D835Y were sensitive to treatment with Ibrance (palbociclib) in culture, demonstrating reduced cell viability and colony formation (PMID: 30544932). | 30544932 |
FLT3 D835Y | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3 D835Y were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
FLT3 D835Y | hematologic cancer | conflicting | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, cultured cells expressing FLT3 D835Y were resistant to treatment with Vanflyta (quizartinib) (PMID: 38231480). | 38231480 |
FLT3 D835Y | hematologic cancer | conflicting | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited growth of transformed hematologic cells expressing FLT3 D835Y in culture (PMID: 31309543). | 31309543 |
FLT3 D835Y | hematologic cancer | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a cell line expressing FLT3 D835Y was resistant to Nexavar (sorafenib) in culture (PMID: 38049555). | 38049555 |
FLT3 D835Y | hematologic cancer | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3 D835Y were resistant to Nexavar (sorafenib)-induced growth inhibition in culture (PMID: 31309543). | 31309543 |
FLT3 D835Y | leukemia | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines over expressing FLT3 D835Y in culture (PMID: 26822154). | 26822154 |
FLT3 D835Y | acute myeloid leukemia | sensitive | E6201 | Preclinical - Cell culture | Actionable | In a preclinical study, E6201 induced apoptosis in blast samples derived from acute myeloid leukemia patients harboring FLT3 D835Y in culture (PMID: 26822154). | 26822154 |
FLT3 D835Y | acute promyelocytic leukemia | predicted - resistant | Tretinoin | Case Reports/Case Series | Actionable | In a clinical case study, a patient with acute promyelocytic leukemia developed meningeal relapse after maintenance therapy with Vesanoid (tretinoin), which was found to be due to a FLT3 D835Y variant (PMID: 27626069). | 27626069 |
FLT3 D835Y | hematologic cancer | sensitive | Pacritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vonjo (pacritinib) inhibited kinase activity and viability in a transformed cell line expressing FLT3 D835Y in culture (PMID: 31102119). | 31102119 |
FLT3 D835Y | hematologic cancer | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) inhibited growth of transformed hematologic cells expressing FLT3 D835Y in culture (PMID: 31309543). | 31309543 |
FLT3 D835Y | hematologic cancer | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) inhibited viability of cultured cells expressing FLT3 D835Y (PMID: 38231480). | 38231480 |
FLT3 D835Y | hematologic cancer | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) resulted in reduced cell viability in transformed cells expressing FLT3 D835Y in culture (PMID: 32040554). | 32040554 |
FLT3 D835Y | hematologic cancer | resistant | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3 D835Y were resistant to Ayvakit (avapritinib)-induced growth inhibition in culture (PMID: 31309543). | 31309543 |
FLT3 D835Y | hematologic cancer | sensitive | Dubermatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Dubermatinib (TP-0903) inhibited growth of transformed cells expressing FLT3 D835Y in culture (PMID: 33268594). | 33268594 |
FLT3 D835Y | hematologic cancer | sensitive | Everolimus + Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination therapy of Ibrance (palbociclib) and Afinitor (everolimus) resulted in a synergistic effect in transformed cells expressing FLT3 D835Y, demonstrating a greater reduced cell viability compared to either agent alone (PMID: 30544932). | 30544932 |
FLT3 D835Y | Advanced Solid Tumor | sensitive | MRX-2843 | Preclinical - Cell culture | Actionable | In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing FLT3 D835Y in culture (PMID: 27158668). | 27158668 |
FLT3 D835Y | acute promyelocytic leukemia | predicted - sensitive | Arsenic trioxide + Cytarabine + Methotrexate + Tretinoin | Case Reports/Case Series | Actionable | In a clinical case study, a patient with acute promyelocytic leukemia harboring FLT3 D835Y demonstrated a complete molecular remission after treatment with Trisenox (arsenic trioxide) and Vesanoid (tretinoin) combined with Cytosar-U (cytarabine) and Methotrexate (PMID: 27626069). | 27626069 |
FLT3 D835Y | hematologic cancer | sensitive | CG-806 | Preclinical - Cell culture | Actionable | In a preclinical study, CG-806 inhibited proliferation of a cell line expressing FLT3 D835Y in culture (PMID: 35499387). | 35499387 |
FLT3 D835Y | acute myeloid leukemia | predicted - sensitive | LAM-003 | Preclinical - Patient cell culture | Actionable | In a preclinical study, patient-derived acute myeloid leukemia cells harboring FLT3 D835Y demonstrated sensitivity to LAM-003 treatment in culture (PMID: 31751472). | 31751472 |
FLT3 D835Y | hematologic cancer | sensitive | Olverembatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Olverembatinib (HQP1351) inhibited growth of transformed cells expressing FLT3 D835Y in culture (PMID: 32247263). | 32247263 |
FLT3 D835Y | hematologic cancer | sensitive | Crenolanib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Crenolanib (CP-868596) and Mekinist (trametinib) synergistically decreased proliferation of transformed cells expressing FLT3 D835Y in culture (PMID: 30651561). | 30651561 |
FLT3 D835Y | hematologic cancer | sensitive | Danusertib + Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Ibrance (palbociclib) and Danusertib (PHA-739358) resulted in a synergistic effect, leading to a greater decrease in cell viability of transformed cells expressing FLT3 D835Y in culture compared to either agent alone (PMID: 30544932). | 30544932 |
FLT3 D835Y | hematologic cancer | sensitive | Alisertib + Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination treatment of Ibrance (palbociclib) and Alisertib (MLN8237) resulted in a synergistic effect in transformed cells expressing FLT3 D835Y, demonstrating a greater reduction in cell viability compared to either agent alone (PMID: 30544932). | 30544932 |
FLT3 D835Y | hematologic cancer | sensitive | SKI-G-801 | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FLT3 D835Y were sensitive to SKI-G-801 in culture, demonstrating inhibition of cell growth and inhibition of Flt3 autophosphorylation (PMID: 24532805). | 24532805 |
FLT3 D835Y | hematologic cancer | sensitive | LT-171-861 | Preclinical - Cell culture | Actionable | In a preclinical study, LT-171-861 inhibited cell viability and decreased FLT3 phosphorylation in transformed cells expressing FLT3 D835Y in culture (PMID: 33391463). | 33391463 |