{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:54:44Z","timestamp":1792652084019,"version":"4.5.0"},"reference-count":133,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Acute myeloid leukemia (AML) is characterized by the clonal expansion of myeloid progenitors blocked at various stages of their differentiation process, and drugs that bypass this differentiation block are therapeutically efficient, as shown by retinoic acid and arsenic trioxide in acute promyelocytic leukemia. However, the successful application of differentiation therapy in APL has not translated into clinical benefit for other non-APL subtypes of AML, in which intensive chemotherapy regimens represent the standard of care. However, the development of molecular studies has led to the identification of therapeutic targets (such as mutated proteins and deregulated pathways) and has led to the generation of a new category of specific pharmacologic agents. Some of these agents, such as inhibitors of mutant isocitrate dehydrogenase (IDH1 and IDH2), lysine-specific demethylase-1 (LSD1), and Menin, have shown the capacity to induce leukemic cell differentiation and with significant therapeutic efficacy.<\/jats:p>","DOI":"10.3390\/cancers17071141","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T13:36:49Z","timestamp":1743169009000},"page":"1141","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Recent Developments in Differentiation Therapy of Acute Myeloid Leukemia"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7900-8942","authenticated-orcid":false,"given":"Ugo","family":"Testa","sequence":"first","affiliation":[{"name":"Department of Oncology, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3593-1230","authenticated-orcid":false,"given":"Germana","family":"Castelli","sequence":"additional","affiliation":[{"name":"Department of Oncology, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3043-6249","authenticated-orcid":false,"given":"Elvira","family":"Pelosi","sequence":"additional","affiliation":[{"name":"Department of Oncology, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1182\/blood.V57.6.1000.1000","article-title":"Terminal differentiation of human promyelocytic leukemic cells in primary culture in response to retinoic acid","volume":"57","author":"Breitman","year":"1981","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1182\/blood.V72.2.567.567","article-title":"Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia","volume":"72","author":"Huang","year":"1988","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1016\/0140-6736(90)93135-C","article-title":"Treatment of first relapse in acute promyelocytic leukemia with all-trans retinoic acid","volume":"336","author":"Degos","year":"1990","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1182\/blood.V76.9.1704.1704","article-title":"All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia, I: Clinical results","volume":"76","author":"Castaigne","year":"1990","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/347558a0","article-title":"The t(15;17) translocation of acute promyelocytic leukemia fuses the retinoic acid receptor alpha geneto a novel transcribed locus","volume":"347","author":"Chomienne","year":"1990","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/0092-8674(93)80044-F","article-title":"The acute promyelocytic leukemia-specific PML-RAR\u03b1 fusion protein inhibits differentiation and promotes survival of myeloid precursor cells","volume":"74","author":"Grignani","year":"1993","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1056\/NEJMoa1300874","article-title":"Retinoic acid and arsenic trioxide for acute promyelocytic leukemia","volume":"369","author":"Avvisati","year":"2013","journal-title":"N. 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