Mutations in epigenetic modifiers in acute myeloid leukemia and their clinical utility

ABSTRACT

Recent studies have identified recurrent mutations in genes that encode proteins crucial in the epigenetic regulation of gene transcription in hematologic malignancies. Somatic mutations in epigenetic modifiers, including IDH1, IDH2, TET2, DNAMT3A, ASXL1, MLL and EZH2 are enriched in patients with acute myeloid leukemia (AML), especially those with intermediate-risk cytogenetics. Here we describe the clinic-biologic features of AML patients with these mutations, their prognostic relevance and potential as therapeutic targets. The epigenetic alterations are present as the early pre-leukemic events and usually remain stable during disease evolution, implying the potential to be biomarkers for minimal residual disease monitoring. The high frequency of mutations in epigenetic modifiers and their prognostic implications shed light on the development of epigenetic therapy.

KEYWORDS:

• Acute myeloid leukemia
• mutation
• epigenetic modifiers
• leukemogenesis
• prognosis
• epigenetic therapy

Financial & competing interests disclosure

This work was partially sponsored by grants MOST,103-2628-B-002-008-MY3, 103-2923-B-002 -001 and 104-2314-B-002 -128-MY4 from the Ministry of Science and Technology (Taiwan), MOHW103-TD-B-111-04 from the Ministry of Health and Welfare (Taiwan). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.