{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:54:43Z","timestamp":1790963683650,"version":"4.1.0"},"reference-count":0,"publisher":"American Society of Hematology","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Although intensified chemotherapy regimens have improved survival of T-cell acute lymphoblastic leukemia (T-ALL) patients, treatment-related toxicities and poor outcomes following relapse highlight the need for alternative therapeutics. Our previous studies showed that leukemia-associated myeloid cells support T-ALL progression, suggesting myeloid cells or associated signals could serve as therapeutic targets. It remains unknown whether leukemia-associated myeloid cells support multiple molecular subtypes of T-ALL, and if so, whether subtype-specific mechanisms are involved. We demonstrate that tumor-associated myeloid cells support survival of both Early T-cell Progenitor (ETP)-like and non-ETP-like T-ALL subtypes from the LMO2 mouse model in vitro and in vivo. Transcriptional profiling and in vitro assays of mouse and human T-ALL reveal that myeloid cells support distinct T-ALL subtypes via different signaling pathways: IL6ST\/STAT3 signaling supports ETP-like T-ALL, while growth factor receptor signaling supports non-ETP-like T-ALL. Notably, both subtypes require AKT activation for myeloid-mediated support, and acute myeloid depletion in vivo induces a common metabolic shift towards oxidative phosphorylation (OxPhos). These findings suggest that myeloid cells promote T-ALL survival via subtype-specific signals that converge on a common pathway regulating metabolism. The shared metabolic adaptation to myeloid cell loss suggests a compensatory mechanism enabling T-ALL persistence under stress. Consistent with this possibility, combining myeloid depletion with OxPhos inhibition reduces survival of mouse and patient T-ALL cells and prolongs leukemic mouse survival more than either single treatment. Our data highlight unique and shared mechanisms by which myeloid cells support T-ALL subtypes and implicate tumor-myeloid interactions and downstream metabolic reprogramming as promising therapeutic targets.<\/jats:p>","DOI":"10.1182\/blood.2026033335","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:57:33Z","timestamp":1790881053000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":0,"title":["Leukemia-associated myeloid cells support distinct T-ALL subtypes via unique signals converging on metabolic alterations"],"prefix":"10.1182","author":[{"given":"Seohee","family":"Nam","sequence":"first","affiliation":[{"name":"The University of Texas at Austin, Austin, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1043-864X","authenticated-orcid":false,"given":"Doris Narki","family":"Tetteh","sequence":"additional","affiliation":[{"name":"The University of Texas at Austin, Austin, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3176-8079","authenticated-orcid":false,"given":"Elizabeth M","family":"Kappil","sequence":"additional","affiliation":[{"name":"The University of Texas at Austin, Austin, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor D.","family":"Mauk","sequence":"additional","affiliation":[{"name":"The University of Texas at Austin, Austin, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F","family":"Moore","sequence":"additional","affiliation":[{"name":"The University of Texas at Austin, Austin, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhivya","family":"Arasappan","sequence":"additional","affiliation":[{"name":"The University of Texas at Austin, Austin, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0380-3549","authenticated-orcid":false,"given":"Dennis C","family":"Wylie","sequence":"additional","affiliation":[{"name":"The University of Texas at Austin, Austin, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3044-4887","authenticated-orcid":false,"given":"Aram","family":"Lyu","sequence":"additional","affiliation":[{"name":"The University of Texas at Austin, Austin, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5253-9927","authenticated-orcid":false,"given":"Ryan S.","family":"Humphrey","sequence":"additional","affiliation":[{"name":"The University of Texas at AUstin, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3547-448X","authenticated-orcid":false,"given":"Xiaolu A","family":"Cambronne","sequence":"additional","affiliation":[{"name":"The University of Texas at Austin, Austin, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terzah M.","family":"Horton","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine\/Dan L. Duncan Cancer Center and Texas Children's Cancer Center, Houston, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1697-1755","authenticated-orcid":false,"given":"Lauren I R","family":"Ehrlich","sequence":"additional","affiliation":[{"name":"The University of Texas at Austin, Austin, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2026,10,1]]},"container-title":["Blood Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2026033335\/2593715\/blood.2026033335.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2026033335\/2593715\/blood.2026033335.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:29:54Z","timestamp":1790962194000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/doi\/10.1182\/blood.2026033335\/571346\/Leukemia-associated-myeloid-cells-support-distinct"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1182\/blood.2026033335","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]},"article-number":"blood.2026033335"}}