Molecular Profile Detail

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Profile Name DNMT3A R882H NRAS G12D
Gene Variant Detail

DNMT3A R882H (loss of function)

NRAS G12D (loss of function)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
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