{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T23:37:57Z","timestamp":1788910677186,"version":"build-2803163510"},"reference-count":104,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T00:00:00Z","timestamp":1676246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Research and Development expenses grant","award":["2021-A-11"],"award-info":[{"award-number":["2021-A-11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypomethylating agents (HMAs) have been used for decades in the treatment of hematologic neoplasms, and now, have gathered attention again in terms of their combination with potent molecular-targeted agents such as a BCL-6 inhibitor venetoclax and an IDH1 inhibitor ivosidenib, as well as a novel immune-checkpoint inhibitor (anit-CD47 antibody) megrolimab. Several studies have shown that leukemic cells have a distinct immunological microenvironment, which is at least partially due to genetic alterations such as the TP53 mutation and epigenetic dysregulation. HMAs possibly improve intrinsic anti-leukemic immunity and sensitivity to immune therapies such as PD-1\/PD-L1 inhibitors and anti-CD47 agents. This review describes the immuno-oncological backgrounds of the leukemic microenvironment and the therapeutic mechanisms of HMAs, as well as current clinical trials of HMAs and\/or venetoclax-based combination therapies.<\/jats:p>","DOI":"10.3390\/ijms24043727","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T04:32:58Z","timestamp":1676262778000},"page":"3727","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Immuno-Oncology and Genomic Aspects of DNA-Hypomethylating Therapeutics in Acute Myeloid Leukemia"],"prefix":"10.3390","volume":"24","author":[{"given":"Akiko","family":"Urabe","sequence":"first","affiliation":[{"name":"Department of Hematology, National Cancer Center Hospital East, Kashiwa 277-8577, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5725-7187","authenticated-orcid":false,"given":"SungGi","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Hematology, National Cancer Center Hospital East, Kashiwa 277-8577, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Minami","sequence":"additional","affiliation":[{"name":"Department of Hematology, National Cancer Center Hospital East, Kashiwa 277-8577, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1111\/j.1365-2141.2006.06476.x","article-title":"The Haematopoietic Cell Transplantation Comorbidity Index Score Is Predictive of Early Death and Survival in Patients over 60 Years of Age Receiving Induction Therapy for Acute Myeloid Leukaemia","volume":"136","author":"Giles","year":"2007","journal-title":"Br. 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