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Abstract
Over the past decades, our molecular understanding of acute myeloid leukemia (AML) pathogenesis dramatically increased, thanks also to the advent of next-generation sequencing (NGS) technologies. Many of these findings, however, have not yet translated into new prognostic markers or rationales for treatments. We now know that AML is a highly heterogeneous disease characterized by a very low mutational burden. Interestingly, the few mutations identified mainly reside in epigenetic regulators, which shape and define leukemic cell identity. In the light of these discoveries and given the increasing number of drugs targeting epigenetic regulators in clinical development and testing, great interest is emerging for the use of small molecules targeting leukemia epigenome. Together with their effects on leukemia cell-intrinsic properties, such as proliferation and survival, epigenetic drugs may affect the way leukemic cells communicate with the surrounding components of the tumor and immune microenvironment. Here, we review current knowledge on alterations in the AML epigenetic landscape and discuss the promises of epigenetic therapies for AML treatment. Finally, we summarize emerging molecular studies elucidating how epigenetic rewiring in cancer cells may as well exert immune-modulatory functions, boost the immune system, and potentially contribute to better patient outcomes.
Highlights
Acute myeloid leukemia (AML) is an aggressive blood cancer, characterized by the uncontrolled proliferation of poorly differentiated hematopoietic stem and progenitor cells
AML is a highly heterogeneous cancer type often associated with bad prognosis, with the minority of patients being cured without allo-HCT and for which new therapeutic approaches are urgently needed
We provide a comprehensive overview of studies documenting the effects of epigenetic aberrations in AML pathogenesis and summarized the most recent clinical efforts reporting safety and efficacy of epigenetic compounds for AML treatment
Summary
Acute myeloid leukemia (AML) is an aggressive blood cancer, characterized by the uncontrolled proliferation of poorly differentiated hematopoietic stem and progenitor cells. Even if disease prognosis has improved over the last decades, mainly thanks to decreased treatmentrelated mortality and wider use of allogeneic hematopoietic cell transplantation (allo-HCT) as consolidation therapy, prognostic classification of AML patients remains inaccurate and therapeutic options for high-risk patient are largely unsatisfactory (Dohner et al, 2015)
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