Increasing H3K9 methylation level reduces the proliferation of leukemic stem cells [bulk RNA-seq of IOX1-treated HM cells]

While a few epigenetic drugs have entered clinical practice, studies focusing on histone post-translational modifications (PTMs) altered in AML remain limited. Here, we used murine HSPCs, murine AML mouse models, human leukemic cell lines, and leukemic patient samples to investigate whether targeting the methylation of histone 3 at lysine 9 (H3K9 methylation) affects HSPCs upon aging and leukemogenesis and might represent a possible target.

Our data show that H3K9 methylation changes upon aging in HSPCs and is linked to a pre-malignant phenotype. Low levels of H3K9 methylation in leukemic cells are required to maintain proliferative capacities in vitro. Increasing H3K9 methylation reduces the leukemogenesis of both young and aged murine and patient-derived leukemic cells.