{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T20:45:13Z","timestamp":1780433113628,"version":"3.54.1"},"reference-count":51,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01CA076167"],"award-info":[{"award-number":["R01CA076167"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01CA264983"],"award-info":[{"award-number":["R01CA264983"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U01CA224766"],"award-info":[{"award-number":["U01CA224766"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Paceline Award"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cells"],"abstract":"<jats:p>The development of FGFR1-driven stem cell leukemia and lymphoma syndrome (SCLL) in mouse models is accompanied by an increase in highly heterogenous myeloid derived suppressor cells (MDSCs), which promote immune evasion. To dissect this heterogeneity, we used a combination of CyTOF and scRNA-Seq to define the phenotypes and genotypes of these MDSCs. CyTOF demonstrated increased levels of circulating macrophages in the peripheral blood of leukemic mice, and flow cytometry demonstrated that these macrophages were derived from Ly6CHi M-MDSC as well as the Ly6CInt and Ly6CLow monocytic populations. Consistently, scRNA-Seq analysis demonstrated the accumulation of non-classical monocytes (ncMono) during leukemia progression, which also express macrophage markers. These leukemia-induced macrophages show continuous transcriptional reprogramming during leukemia progression, with the upregulation of cellular stress response genes Hspa1a and Hspa1b and inflammation-related gene Nfkbia. Trajectory analysis revealed a transition from classical monocytes (cMono) to ncMono, and potential genes orchestrating this transition process have been identified. Furthermore, T-cell suppression assays demonstrated the immune suppressive abilities of leukemia-induced circulatory macrophages. Targeting these macrophages with the GW2580 CSF1R inhibitor leads to restored immune surveillance and improved survival. Overall, we demonstrate that circulating macrophages are responsible, at least in part, for the immune suppression in SCLL leukemia models, and targeting macrophages in this system improves the survival of leukemic mice.<\/jats:p>","DOI":"10.3390\/cells14191533","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T14:16:29Z","timestamp":1759241789000},"page":"1533","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genomic Analysis Defines Increased Circulating, Leukemia-Induced Macrophages That Promote Immune Suppression in Mouse Models of FGFR1-Driven Leukemogenesis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0616-5565","authenticated-orcid":false,"given":"Ting","family":"Zhang","sequence":"first","affiliation":[{"name":"Georgia Cancer Center, 1410 Laney Walker Blvd., Augusta, GA 30912, USA"},{"name":"Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuko","family":"Matsunaga","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, 1410 Laney Walker Blvd., Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaocui","family":"Lu","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, 1410 Laney Walker Blvd., Augusta, GA 30912, USA"},{"name":"Department of Stomatology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Fang","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, 1410 Laney Walker Blvd., Augusta, GA 30912, USA"},{"name":"Department of Stomatology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nandini","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7888-5019","authenticated-orcid":false,"given":"Ahmad","family":"Alimadadi","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie F.","family":"Mori","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, 1410 Laney Walker Blvd., Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuexiu","family":"Fang","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, 1410 Laney Walker Blvd., Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biology and Psychology, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1137-3390","authenticated-orcid":false,"given":"Huidong","family":"Shi","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, 1410 Laney Walker Blvd., Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Litao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine C.","family":"Hedrick","sequence":"additional","affiliation":[{"name":"Immunology Center of Georgia, 1410 Laney Walker Blvd., Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1916-0410","authenticated-orcid":false,"given":"Bo","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5127-9211","authenticated-orcid":false,"given":"Tianxiang","family":"Hu","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, 1410 Laney Walker Blvd., Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John K.","family":"Cowell","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, 1410 Laney Walker Blvd., Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.humpath.2009.11.003","article-title":"8p11 myeloproliferative syndrome: A review","volume":"41","author":"Jackson","year":"2010","journal-title":"Hum. 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