biostudies-literatureSan Jose-Eneriz E"la Caixa" Foundation (Caixa Foundation)Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)International Myeloma FoundationMinistry of Economy and Competitiveness | Instituto de Salud Carlos IIIDepartamento de Educación, Gobierno de Navarra"la Caixa" FoundationDepartamento de Educación, Gobierno de Navarra (Department of Education, Government of Navarra)International Myeloma Foundation (IMF)5570https://www.ebi.ac.uk/biostudies/studies/S-EPMC11219871biostudies-literatureUnknown15(1)Despite the development of novel therapies for acute myeloid leukemia, outcomes remain poor for most patients, and therapeutic improvements are an urgent unmet need. Although treatment regimens promoting differentiation have succeeded in the treatment of acute promyelocytic leukemia, their role in other acute myeloid leukemia subtypes needs to be explored. Here we identify and characterize two lysine deacetylase inhibitors, CM-444 and CM-1758, exhibiting the capacity to promote myeloid differentiation in all acute myeloid leukemia subtypes at low non-cytotoxic doses, unlike other commercial histone deacetylase inhibitors. Analyzing the acetylome after CM-444 and CM-1758 treatment reveals modulation of non-histone proteins involved in the enhancer-promoter chromatin regulatory complex, inclNature communicationsEpigenetic-based differentiation therapy for Acute Myeloid Leukemia.PMC1121987144/2021; 0011-1411-2022-000068Brian van NovisPI20/01306, PI23/00488PI19/01352, PI22/00947GN2023/11CB16/12/00369GR-NET NORMAL-HIT HR20-00871Garate LValcarcel LVMartinez-Calle NLarrayoz MJCalasanz MJVilas-Zornoza ASan Martin-Uriz PBarrena NHilscher SSchutkowski MMunoz JMartin-Subero JITamariz-Amador LERabal OGomez-Echarte NOyarzabal JGimenez-Camino NSaez EIsasa MCharalampopoulou SAgirre XSan Jose-Eneriz EProsper FAlfonso-Pierola APaiva BGarcia FPerez-Ruiz AAlignani DPineda-Lucena AMiranda EfalseEpigenetic-based differentiation therapy for Acute Myeloid Leukemia.Despite the development of novel therapies for acute myeloid leukemia, outcomes remain poor for most patients, and therapeutic improvements are an urgent unmet need. Although treatment regimens promoting differentiation have succeeded in the treatment of acute promyelocytic leukemia, their role in other acute myeloid leukemia subtypes needs to be explored. Here we identify and characterize two lysine deacetylase inhibitors, CM-444 and CM-1758, exhibiting the capacity to promote myeloid differentiation in all acute myeloid leukemia subtypes at low non-cytotoxic doses, unlike other commercial histone deacetylase inhibitors. Analyzing the acetylome after CM-444 and CM-1758 treatment reveals modulation of non-histone proteins involved in the enhancer-promoter chromatin regulatory complex, incl2024-01-01T00:00:00Z2024 Jul2026-06-03T00:25:22.953Z2025-04-06T11:36:12.428ZS-EPMC112198713895605310.1038/s41467-024-49784-y