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|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).|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|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||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||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 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||myelofibrosis||not applicable||N/A||Guideline||Prognostic||DNMT3A mutations are associated with inferior overall survival in patients with primary myelofibrosis (NCCN.org).||detail...|
|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||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 + 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|