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These epigenetic modifications can affect the capacity of hematopoietic cells to self-renew or differentiate, which can lead to transformation. Aberrant histone modifications contribute to the derepression of self-renewal genes such as HOXA\/B and MEIS1 in committed hematopoietic progenitors, which is considered a key mechanism of leukemogenesis in MLL-rearranged (MLL-r) and NPM1-mutated AML. As regulators of some of the key histone modifications in this disease, the menin-KMT2A and polycomb repressive (PRC1\/2) complexes have been identified as promising targets for the treatment of AML. This review explores recent discoveries of how leukemic cells hijack these complexes and their interactions with other chromatin regulators to promote disease progression. We also discuss inhibitors targeting these complexes that have demonstrated therapeutic efficacy in preclinical and clinical studies and propose novel therapeutic combinations targeting the KMT2A and PRC1\/2 broader interacting networks to overcome issues of resistance to existing monotherapies.<\/jats:p>","DOI":"10.1093\/stcltm\/szae089","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T18:53:02Z","timestamp":1732819982000},"source":"Crossref","is-referenced-by-count":19,"title":["Targeting chromatin modifying complexes in acute myeloid leukemia"],"prefix":"10.1093","volume":"14","author":[{"given":"Alexandra","family":"Schurer","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Albert Einstein College of Medicine , Bronx, NY 10461 ,","place":["United States"]},{"name":"The Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine, Albert Einstein College of Medicine , Bronx, NY 10461 ,\u00a0","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shira G","family":"Glushakow-Smith","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Albert Einstein College of Medicine , Bronx, NY 10461 ,","place":["United States"]},{"name":"The Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine, Albert Einstein College of Medicine , Bronx, NY 10461 ,\u00a0","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1367-1167","authenticated-orcid":false,"given":"Kira","family":"Gritsman","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Albert Einstein College of Medicine , Bronx, NY 10461 ,","place":["United States"]},{"name":"The Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine, Albert Einstein College of Medicine , Bronx, NY 10461 ,\u00a0","place":["United States"]},{"name":"Department of Medical Oncology, Albert Einstein College of Medicine, Montefiore Medical Center , Bronx, NY 10461 ,","place":["United States"]},{"name":"Center for Tumor Dormancy, Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine , Bronx, NY 10461,","place":["United States"]},{"name":"Marilyn and Stanley M. 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