Chromatin Complexes Maintain Self-Renewal of Myeloid Progenitors in AML: Opportunities for Therapeutic Intervention

Specific subgroups of acute myeloid leukemia (AML), including those containing MLL rearrangements and NPM1c mutations, possess characteristic stem cell-like gene expression profiles. These expression programs are highly dependent on components of the MLL histone methyltransferase complex, including Menin and DOT1L. Understanding the chromatin-based mechanisms through which cancer cells subvert certain aspects of normal stem cell biology helped identify specific vulnerabilities and trans- late them into targeted therapy approaches. Exciting progress has been made in the development of small-molecule inhibitors target-ing this epigenetic machinery in leukemia cells and prompted the development of clinical trials in patients with hematologic malig-nancies.