{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:06:19Z","timestamp":1791839179026,"version":"4.3.4"},"reference-count":57,"publisher":"American Society for Clinical Investigation","issue":"15","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":41,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01CA173852,R01CA134777,R01HL146137,R01HL140961"],"award-info":[{"award-number":["R01CA173852,R01CA134777,R01HL146137,R01HL140961"]}]},{"DOI":"10.13039\/100005968","name":"Leukemia Research Foundation","doi-asserted-by":"crossref","award":["1306942"],"award-info":[{"award-number":["1306942"]}],"id":[{"id":"10.13039\/100005968","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001445","name":"Alex\u2019s Lemonade Stand Foundation for Childhood Cancer","doi-asserted-by":"crossref","award":["1349722"],"award-info":[{"award-number":["1349722"]}],"id":[{"id":"10.13039\/100001445","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Cancer Institute","award":["U54CA196519"],"award-info":[{"award-number":["U54CA196519"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,3]]},"abstract":"<jats:p>\n                    Obesity is increasingly implicated in hematopoietic malignancies, yet its role in mutation-driven myeloid leukemias remains unclear. Using UK Biobank data from over 440,000 individuals, we found obesity traits including elevated BMI and waist-to-hip ratio were associated with type 2 diabetes, increased plasma IL-17A levels, reduced glucagon-like peptide 1 receptor (GLP-1R) expression, and heightened risk of myeloid malignancies. Transplantation of protein tyrosine phosphatase nonreceptor type 11 (\n                    <jats:italic>PTPN11<\/jats:italic>\n                    ) (\n                    <jats:italic>\n                      Shp2\n                      <jats:sup>E76K\/+<\/jats:sup>\n                    <\/jats:italic>\n                    ) mutant hematopoietic stem\/progenitor cells into obese mice demonstrated that metabolic inflammation accelerated leukemogenesis via myeloid cell expansion, lipid metabolic rewiring, IL-17A activation, and accumulation of M2-like tumor-associated macrophages (TAMs), accompanied by T cell exhaustion and impaired antigen presentation. Notably, dual therapy with an anti\u2013IL-17A antibody and a GLP-1R agonist reversed these effects by reducing M2-like TAMs, restoring Ciita-dependent antigen presentation and Tyk2-mediated IFN-\u03b3 signaling, reactivating T cell responses, and reducing leukemic burden. These findings establish IL-17A\u2013driven, metabolism-coupled immunosuppression as a mechanistic link between obesity and protein tyrosine phosphatase 2\u2013mutant (SHP2-mutant) myeloid leukemias, highlighting a tractable therapeutic strategy for patients with obesity at high risk for other diseases and their complications.\n                  <\/jats:p>\n                  <jats:p\/>\n                  <jats:p>Obesity fuels inflammation that accelerates PTPN11-mutant leukemia by suppressing anti-tumor immunity; targeting IL-17A and GLP-1R reverses this effect and reduces leukemic burden.<\/jats:p>","DOI":"10.1172\/jci202856","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T16:06:53Z","timestamp":1782230813000},"source":"Crossref","is-referenced-by-count":2,"title":["Targeting GLP-1R and IL-17A suppresses obesity-induced leukemia in an oncogenic PTPN11 mutation\u2013driven model"],"prefix":"10.1172","volume":"136","author":[{"given":"Reuben","family":"Kapur","sequence":"first","affiliation":[{"name":"Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine (IUSM), Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linke","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA."},{"name":"Program in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6039-461X","authenticated-orcid":true,"given":"Rahul","family":"Kanumuri","sequence":"additional","affiliation":[{"name":"Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of 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