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We integrated clinical and genomic profiling in 132 newly diagnosed or relapsed\/refractory AML patients treated with HMA\u2010Venetoclax and performed single\u2010cell RNA sequencing and T cell receptor (TCR) profiling in 10 newly diagnosed cases to define cellular and immune correlates of response. Response rates and survival aligned with published data. DNA Sequencing confirmed the favorable impact of IDH2 and the poor prognosis of TP53 mutations. scRNA\u2010seq and TCR analysis showed that responders exhibited expansion of cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, increased TCR clonal diversity, and activation of antigen\u2010presentation pathways. Nonresponders displayed baseline inflammatory signaling, impaired myeloid maturation, and a suppressive microenvironment enriched in IDO1\n                    <jats:sup>+<\/jats:sup>\n                    dendritic cells. Resistant AMLs showed stem\u2010like dedifferentiation and sustained EMT. LAG\u20103 expression marked dysfunctional T cell states and emerged as a potential biomarker and therapeutic target.\n                  <\/jats:p>","DOI":"10.1002\/hem3.70498","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:26:56Z","timestamp":1791908816000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune and cellular determinants of response to HMA\u2010venetoclax regimens in acute myeloid leukemia"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5126-9657","authenticated-orcid":false,"given":"Alfredo","family":"Marchetti","sequence":"first","affiliation":[{"name":"Department of Oncology and Hematology\u2010Oncology University of Milan Milan 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Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Marella","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hematology\u2010Oncology University of Milan Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Maeda","sequence":"additional","affiliation":[{"name":"Hematology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9348-1792","authenticated-orcid":false,"given":"Antonio","family":"Matera","sequence":"additional","affiliation":[{"name":"Hematology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Calvi","sequence":"additional","affiliation":[{"name":"Hematology Unit, 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