{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:48:05Z","timestamp":1792590485364,"version":"4.5.0"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cancer Research UK","award":["RCCASF-Nov22\/100001"],"award-info":[{"award-number":["RCCASF-Nov22\/100001"]}]},{"name":"Oglesby Charitable Trust","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Cancer Research UK","award":["C5759\/A27445"],"award-info":[{"award-number":["C5759\/A27445"]}]},{"name":"Cancer Research UK","award":["C147\/A25254"],"award-info":[{"award-number":["C147\/A25254"]}]},{"name":"Leukemia and Lymphoma Society","award":["8046-24"],"award-info":[{"award-number":["8046-24"]}]},{"name":"Blood Cancer UK","award":["23026"],"award-info":[{"award-number":["23026"]}]},{"name":"Institut National du Cancer","award":["PLBIO24-195"],"award-info":[{"award-number":["PLBIO24-195"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Chronic myelomonocytic leukemia (CMML) is a hematological neoplasm characterized by expansion of malignant monocytes. However, as a stem cell neoplasm, the disease clone comprises most blood lineages, including granulocytes. To investigate their pathogenic contribution, we performed extensive phenotypic, transcriptomic and functional characterization of CMML granulocytes. These cells exhibited reduced granularity and impaired maturation, the latter of which is associated with poor prognosis. Functionally, CMML granulocytes displayed reduced phagocytic capacity and impaired NETosis, together with aberrant gene expression programs. Notably,\n                    <jats:italic>RETN<\/jats:italic>\n                    , encoding the chemokine resistin, was uniquely upregulated in CMML granulocytes. Accordingly, resistin levels were 10-fold higher in CMML plasma, correlating with inferior survival. Ex vivo exposure to resistin directly blocked monocyte maturation and macrophage differentiation, partly via TLR4 interaction, recapitulating the classical monocytosis repartitioning phenotype that characterizes CMML. Resistin-treated monocytes upregulated gene signatures related to immune suppression and myeloid-derived suppressor cell phenotype. Consistent with these findings, CMML patients displayed higher Treg proportions and Th2\/Th1 ratios. Furthermore, we demonstrated that resistin directly skews the Th2\/Th1 ratio via binding to monocytes. Thus, CMML granulocytes produce high levels of resistin, which contributes to defective monocyte maturation and induction of myeloid-derived suppressor cell features in monocytes, thereby fostering an immune-suppressive state in this disease.\n                  <\/jats:p>","DOI":"10.1172\/jci201335","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:23:20Z","timestamp":1792589000000},"source":"Crossref","is-referenced-by-count":0,"title":["Granulocyte-derived Resistin Inhibits Monocyte Maturation and Promotes an Immunosuppressive Phenotype in Chronic Myelomonocytic Leukemia Monocytes"],"prefix":"10.1172","author":[{"given":"Nathan J.","family":"Hull","sequence":"first","affiliation":[{"name":"Epigenetics of Haematopoiesis Laboratory, Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Cant","sequence":"additional","affiliation":[{"name":"Epigenetics of Haematopoiesis Laboratory, Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Guest","sequence":"additional","affiliation":[{"name":"Epigenetics of Haematopoiesis Laboratory, Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hung","family":"Wang","sequence":"additional","affiliation":[{"name":"Epigenetics of Haematopoiesis Laboratory, Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Gurashi","sequence":"additional","affiliation":[{"name":"Epigenetics of Haematopoiesis Laboratory, Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Paredes","sequence":"additional","affiliation":[{"name":"Epigenetics of Haematopoiesis Laboratory, Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Rivera Rivera","sequence":"additional","affiliation":[{"name":"Epigenetics of Haematopoiesis Laboratory, Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Revekka","family":"Lefkati","sequence":"additional","affiliation":[{"name":"Epigenetics of Haematopoiesis Laboratory, Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector","family":"Huerga Encabo","sequence":"additional","affiliation":[{"name":"Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Chin","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Hematology, National Taiwan University Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwei-Fang","family":"Tien","sequence":"additional","affiliation":[{"name":"Division of Hematology, National Taiwan University Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Sellers","sequence":"additional","affiliation":[{"name":"Computational Biology Support Team, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhakar","family":"Sahoo","sequence":"additional","affiliation":[{"name":"Computational Biology Support Team, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Bonnet","sequence":"additional","affiliation":[{"name":"Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Solary","sequence":"additional","affiliation":[{"name":"INSERM U1287, Gustave Roussy Cancer Center, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothee","family":"Selimoglu-Buet","sequence":"additional","affiliation":[{"name":"INSERM U1287, Gustave Roussy Cancer Center, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H.","family":"Wiseman","sequence":"additional","affiliation":[{"name":"Epigenetics of Haematopoiesis Laboratory, Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran","family":"Batta","sequence":"additional","affiliation":[{"name":"Epigenetics of Haematopoiesis Laboratory, Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,10,15]]},"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.jci.org\/articles\/view\/201335\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:23:22Z","timestamp":1792589002000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.jci.org\/articles\/view\/201335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,15]]},"references-count":0,"alternative-id":["10.1172\/JCI201335"],"URL":"https:\/\/doi.org\/10.1172\/jci201335","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,15]]}}}