期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 7, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2019.00207
关键词
acute myeloid leukemia; epigenetics; therapy; immune activation; chromatin
资金
- San Raffaele Hospital
- Italian Ministry of Health [RF-2011-02351998, RF-2011-02348034]
- Associazione Italiana perla Ricerca sul Cancro [14162, 22197]
- DKMS Mechtild Harf Foundation (DKMS Mechtild Harf Research Grant 2015)
- Telethon (TIGET grant) [E5]
- Career Development Award from Human Frontier Science Program (HFSP)
- Advanced Research Grant from the European Hematology Association (EHA)
- Hollis Brownstein Research Grant from Leukemia Research Foundation (LRF)
- Interstellar Initiative on Healthy Longevity from New York Academy of sciences (NYAS)
- Japan Agency for Medical Research and Development (AMED)
- IBSA Foundation
- Italian Ministry of Health (TRANSCAN HLALOSS)
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.
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