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Gene | DNMT3A |
Variant | loss |
Impact List | unknown |
Protein Effect | loss of function |
Gene Variant Descriptions | DNMT3A loss indicates loss of the DNMT3A gene, mRNA, and protein. |
Associated Drug Resistance | |
Category Variants Paths |
DNMT3A mutant DNMT3A inact mut DNMT3A loss |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
DNMT3A loss TET2 loss | acute myeloid leukemia | sensitive | Olaparib | Preclinical - Cell culture | Actionable | In a preclinical study, Lynparza (olaparib) inhibited colony formation in murine acute myeloid leukemia cells harboring TET2 and DNMT3A loss along wtih various oncogenic tyrosine kinase mutations in culture (PMID: 34215619). | 34215619 |
DNMT3A loss TET2 loss | acute myeloid leukemia | sensitive | Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, Talzenna (talazoparib) decreased colony formation in murine acute myeloid leukemia cells harboring TET2 and DNMT3A loss along with a FLT3-ITD mutation in culture (PMID: 34215619). | 34215619 |
DNMT3A loss FLT3 exon 14 ins TET2 loss | acute myeloid leukemia | sensitive | Olaparib + Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Lynparza (olaparib) and Vanflyta (quizartinib) decreased colony formation in mouse acute myeloid leukemia cells harboring a FLT3-ITD mutation and TET2 and DNMT3A loss in culture (PMID: 34215619). | 34215619 |
DNMT3A loss FLT3 exon 14 ins TET2 loss | acute myeloid leukemia | sensitive | Doxorubicin + Olaparib + Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Lynparza (olaparib), Adriamycin (doxorubicin), and Vanflyta (quizartinib) increased DNA double-strand breaks and decreased colony formation in mouse acute myeloid leukemia cells harboring a FLT3-ITD mutation and TET2 and DNMT3A loss in culture (PMID: 34215619). | 34215619 |
DNMT3A loss FLT3 exon 14 ins TET2 loss | acute myeloid leukemia | sensitive | Quizartinib + Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Vanflyta (quizartinib) and Talzenna (talazoparib) decreased colony formation in mouse acute myeloid leukemia cells harboring a FLT3-ITD mutation and TET2 and DNMT3A loss in culture (PMID: 34215619). | 34215619 |
DNMT3A loss FLT3 exon 14 ins | acute myeloid leukemia | no benefit | Quizartinib + Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Talzenna (talazaparib) did not enhance the sensitivity of mouse acute myeloid leukemia cells harboring a FLT3-ITD mutation and DNMT3A loss to Vanflyta (quizartinib) treatment compared to Vanflyta (quizartinib) alone in culture (PMID: 34215619). | 34215619 |