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Profile Name | DNMT3A mutant |
Gene Variant Detail | |
Relevant Treatment Approaches |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|---|
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 | 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 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 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 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT03365661 | Phase II | ALT-803 | QUILT-3.034: Non-Myeloablative TCRa/b Deplete Haplo HSCT With Post ALT-803 for AML | Withdrawn | USA | 0 |
NCT04708054 | Phase II | Busulfan + Cladribine + Fludarabine + Thiotepa + Venetoclax | Venetoclax, Busulfan, Cladribine, and Fludarabine for the Treatment of High-Risk Acute Myeloid Leukemia or Myelodysplastic Syndrome | Recruiting | USA | 0 |