{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:02:29Z","timestamp":1747184549694,"version":"3.40.5"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T00:00:00Z","timestamp":1671408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In chronic lymphocytic leukemia (CLL), the immune system is skewed towards a suppressive milieu. Levels of thrombopoietin (TPO), promoting cellular immune regulatory activity in immune thrombocytopenic purpura, were shown to be elevated in CLL patients. This study explored TPO as a potential immunomodulator, supporting CLL progression. We evaluated CLL cell\u2010induced expression of TPO receptor (TPO\u2010R) on T\u2010cells and effects of its activation on T\u2010cell responses. CLL cell involvement in TPO generation was also assessed. Baseline TPO\u2010R expression on CD4\u2009+\u2009T\u2010cells was found to be higher in CLL patients than in healthy controls (HC). Exposure of HC\u2010T\u2010cells to B\u2010cells, especially to CLL\u2010B\u2010cells stimulated with B\u2010cell activating molecules, resulted in enhanced TPO\u2010R expression on T\u2010cells. CLL\u2010T\u2010cell stimulation with TPO reduced their proliferation and expanded the regulatory T\u2010cell (Treg) population. At baseline, phosphorylation of STAT5, known to impact the Treg phenotype, was elevated in CLL\u2010T\u2010cells relative to those of HC. Exposure to TPO further enhanced STAT5 phosphorylation in CLL\u2010T\u2010cells, possibly driving the observed Treg expansion. The CLL immune milieu is involved in promotion of inhibitory features in T\u2010cells through increased TPO\u2010R levels and TPO\u2010induced intracellular signaling. TPO and its signaling pathway could potentially support immunosuppression in CLL, and may emerge as novel therapeutic targets.<\/jats:p>","DOI":"10.1111\/ejh.13912","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T20:59:25Z","timestamp":1670446765000},"page":"371-378","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In chronic lymphocytic leukemia, activation of the thrombopoietin receptor promotes T\u2010cell inhibitory properties, contributing to immunosuppression"],"prefix":"10.1111","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4897-1466","authenticated-orcid":false,"given":"Shimrit","family":"Ringelstein\u2010Harlev","sequence":"first","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation Rambam Health Care Campus  Haifa Israel"},{"name":"The Ruth and Bruce Rappaport Faculty of Medicine Technion, Israel Institute of Technology  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