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Gene Symbol DNMT3A
Synonyms DNMT3A2 | HESJAS | M.HsaIIIA | TBRS
Gene Description DNMT3A, DNA methyltransferase 3 alpha, mediates DNA methylation and functions in modification of gene expression, and plays a role in hematopoietic differentiation (PMID: 28286768, PMID: 25693834). DNMT3A mutations are frequent in acute myeloid leukemia, and are recurrent in myelodysplastic syndromes (PMID: 28286768, PMID: 28003281).

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
DNMT3A R882H NRAS G12D acute myeloid leukemia sensitive Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, an acute myeloid leukemia cell line xenograft model harboring DNMT3A R882H and NRAS G12D was sensitive to Mekinist (trametinib), demonstrating impaired disease progression and improved survival (PMID: 31164355). 31164355
DNMT3A R882H NRAS G12D acute myeloid leukemia sensitive I-BET151 Preclinical - Cell line xenograft Actionable In a preclinical study, an acute myeloid leukemia cell line harboring DNMT3A R882H and NRAS G12D mutations demonstrated reduced proliferation and downregulation of a DNMT3A R882H associated gene expression profile upon I-BET151 treatment in culture, and I-BET151 treatment delayed the onset of leukemia symptoms and improved survival in xenograft mouse models derived from these cells (PMID: 31164355). 31164355
DNMT3A R882H NRAS G12D acute myeloid leukemia sensitive I-BET151 + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, an acute myeloid leukemia cell line xenograft model harboring DNMT3A R882H and NRAS G12D treated with combined I-BET151 and Mekinist (trametinib) demonstrated impaired disease progression and improved survival superior to either therapy alone (PMID: 31164355). 31164355
DNMT3A mutant acute myeloid leukemia predicted - sensitive Decitabine Clinical Study - Cohort Actionable In a clinical study, acute myeloid leukemia patients harboring DNMT3A mutations demonstrated a greater complete response rate (60% vs 33%) compared to patients with wild-type DNMT3A when treated with frontline hypomethylating agents such as Dacogen (decitabine) (PMID: 27418649). 27418649
DNMT3A mutant acute myeloid leukemia resistant Olaparib Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived acute myeloid leukemia cells harboring a DNMT3A mutation along with FLT3-ITD and NPM1 mutation were resistant to Lynparza (olaparib) in culture (PMID: 34215619). 34215619
DNMT3A mutant myelofibrosis not applicable N/A Guideline Prognostic DNMT3A mutations are associated with inferior overall survival in patients with primary myelofibrosis (NCCN.org). detail...
DNMT3A mutant acute myeloid leukemia not applicable N/A Clinical Study Prognostic In clinical analyses, mutations in DNMT3A were associated with poor prognosis and shorter overall survival in patients with acute myeloid leukemia (PMID: 22490330, PMID: 21881046, PMID: 21670448). 22490330 21881046 21670448
DNMT3A mutant angioimmunoblastic T-cell lymphoma not applicable N/A Guideline Diagnostic DNMT3A mutations aid in the diagnosis of angioimmunoblastic T-cell lymphoma (NCCN.org). detail...
DNMT3A mutant acute myeloid leukemia sensitive Pinometostat Preclinical - Cell line xenograft Actionable In a preclinical study, Pinometostat (EPZ-5676) treatment of acute myeloid leukemia cell lines and xenografts resulted in apoptosis, cell-cycle arrest, and terminal differentiation (PMID: 27335278). 27335278
DNMT3A mut TET2 mut acute myeloid leukemia sensitive Olaparib Preclinical - Patient cell culture Actionable In a preclinical study, Lynparza (olaparib) treatment inhibited colony formation in patient-derived acute myeloid leukemia cells co-harboring a DNMT3A and TET2 mutation along with FLT3-ITD and NPM1 mutation in culture (PMID: 34215619). 34215619
DNMT3A mut FLT3 exon 14 ins TET2 mut acute myeloid leukemia sensitive Olaparib + Quizartinib Preclinical - Patient cell culture Actionable In a preclinical study, the combination of Lynparza (olaparib) and Vanflyta (quizartinib) inhibited colony formation in patient-derived acute myeloid leukemia cells harboring FLT3-ITD and DNMT3A and TET2 mutations along with an NPM1 mutation in culture (PMID: 34215619). 34215619
DNMT3A mut FLT3 exon 14 ins TET2 mut acute myeloid leukemia sensitive Doxorubicin + Olaparib + Quizartinib Preclinical - Patient cell culture Actionable In a preclinical study, the combination of Lynparza (olaparib), Adriamycin (doxorubicin), and Vanflyta (quizartinib) inhibited colony formation in patient-derived acute myeloid leukemia cells harboring FLT3-ITD and DNMT3A and TET2 mutations along with an NPM1 mutation in culture (PMID: 34215619). 34215619
DNMT3A del acute myeloid leukemia resistant Olaparib Preclinical - Cell culture Actionable In a preclinical study, mouse acute myeloid leukemia cells harboring a DNMT3A deletion along with FLT3-ITD mutation were resistant to Lynparza (olaparib) in culture (PMID: 34215619). 34215619
DNMT3A del TET2 del acute myeloid leukemia sensitive Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) inhibited colony formation of mouse acute myeloid leukemia cells harboring TET2 and DNMT3A deletion along with a FLT3-ITD mutation in culture (PMID: 34215619). 34215619
DNMT3A loss acute myeloid leukemia resistant Talazoparib Preclinical - Cell culture Actionable In a preclinical study, mouse acute myeloid leukmia cells harboring DNMT3A loss along with a FLT3-ITD mutation were resistant to Talzenna (talazoparib) in culture (PMID: 34215619). 34215619
DNMT3A loss acute myeloid leukemia resistant Olaparib Preclinical - Cell culture Actionable In a preclinical study, mouse acute myeloid leukemia cells harboring DNMT3A loss along with various oncogenic tyrosine kinase mutations were resistant to Lynparza (olaparib) 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 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 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