{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T10:29:26Z","timestamp":1794047366954,"version":"4.8.0"},"reference-count":47,"publisher":"Ferrata Storti Foundation (Haematologica)","issue":"9","license":[{"start":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T00:00:00Z","timestamp":1596067200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/legalcode"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["haematol"],"abstract":"<jats:p>Phenotypic characterization of T cells in myelofibrosis (MF) is intriguing owing to increased inflammation, markedly elevated pro-inflammatory cytokines, and altered distribution of T-cell subsets. Constitutive activation of Janus kinase-2 (JAK2) in the majority of MF patients contributes to the expression of the programmed cell death protein-1 (PD1) and T-cell exhaustion. We wondered whether T-cell activation affects treatment outcome of patients with MF and sought to determine whether the JAK1\/2 inhibitor ruxolitinib affects the activation of T-cell subsets. T cells from 47 MF patients were analyzed and the percent of either helper (CD4+) or cytotoxic (CD8+) naive, central memory, effector memory, or effector T cells; and fractions of PD1-expressing cells in each subset were assessed. An increased number of T cells coexpressing CD4\/PD1 and CD8\/PD1 in MF compared to healthy controls (n=28) was found, and the T cells were significantly skewed toward an effector phenotype in both CD4+ and CD8+ subsets, consistent with a shift from a quiescent to an activated state. Over the course of ruxolitinib treatment, the distribution of aberrant T-cell subsets significantly reversed towards resting cell phenotypes. CD4+ and CD8+ subsets at baseline correlated with monocyte and platelet counts, and their PD1-positive fractions correlated with leukocyte counts and spleen size. Low numbers of PD1+\/CD4+ and PD1+\/CD8+ cells were associated with complete resolution of palpable splenomegaly and improved survival rate, suggesting that low levels of exhausted T cells confer a favorable response to ruxolitinib treatment.<\/jats:p>","DOI":"10.3324\/haematol.2020.249441","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T14:40:38Z","timestamp":1596120038000},"page":"2384-2396","source":"Crossref","is-referenced-by-count":18,"title":["Altered T-cell subset repertoire affects treatment outcome of patients with myelofibrosis"],"prefix":"10.3324","volume":"106","author":[{"family":"Ivo Veletic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Sanja Prijic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Taghi Manshouri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Graciela M. Nogueras-Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Srdan Verstovsek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Zeev Estrov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1856","published-online":{"date-parts":[[2020,7,30]]},"reference":[{"key":"28879","doi-asserted-by":"crossref","unstructured":"Barosi G. An immune dysregulation in MPN. Curr Hematol Malig Rep. 2014; 9(4):331-339.","DOI":"10.1007\/s11899-014-0227-0"},{"key":"28880","doi-asserted-by":"crossref","unstructured":"Hasselbalch HC, Bjorn ME. MPNs as inflammatory diseases: the evidence, consequences, and perspectives. Mediators Inflamm. 2015; 2015:102476.","DOI":"10.1155\/2015\/102476"},{"key":"28881","doi-asserted-by":"crossref","unstructured":"Vainchenker W, Kralovics R.. Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms. Blood. 2017; 129(6):667-679.","DOI":"10.1182\/blood-2016-10-695940"},{"key":"28882","doi-asserted-by":"crossref","unstructured":"Hasselbalch HC. The role of cytokines in the initiation and progression of myelofibrosis. Cytokine Growth Factor Rev. 2013; 24(2):133-145.","DOI":"10.1016\/j.cytogfr.2013.01.004"},{"key":"28883","doi-asserted-by":"crossref","unstructured":"Veletic I, Manshouri T, Newberry KJ, Garnett J, Verstovsek S, Estrov Z.. Pentraxin- 3 plasma levels correlate with tumour burden and overall survival in patients with primary myelofibrosis. Br J Haematol. 2018; 185(2):382-386.","DOI":"10.1111\/bjh.15528"},{"key":"28884","doi-asserted-by":"crossref","unstructured":"Villarino AV, Kanno Y, O\u2019Shea JJ. Mechanisms and consequences of Jak-STAT signaling in the immune system. 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JAK1\/2 inhibition impairs T cell function invitro and in patients with myeloproliferative neoplasms. Br J Haematol. 2015; 169(6):824-833.","DOI":"10.1111\/bjh.13373"},{"key":"28889","doi-asserted-by":"crossref","unstructured":"Keohane C, Kordasti S, Seidl T. JAK inhibition induces silencing of T helper cytokine secretion and a profound reduction in T regulatory cells. Br J Haematol. 2015; 171(1):60-73.","DOI":"10.1111\/bjh.13519"},{"key":"28890","doi-asserted-by":"crossref","unstructured":"Holmstrom MO, Riley CH, Svane IM, Hasselbalch HC, Andersen MH. The CALR exon 9 mutations are shared neoantigens in patients with CALR mutant chronic myeloproliferative neoplasms. Leukemia. 2016; 30(12):2413-2416.","DOI":"10.1038\/leu.2016.233"},{"key":"28891","doi-asserted-by":"crossref","unstructured":"Holmstrom MO, Hjortso MD, Ahmad SM. The JAK2V617F mutation is a target for specific T cells in the JAK2V617F-positive myeloproliferative neoplasms. 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Longterm treatment with ruxolitinib for patients with myelofibrosis: 5-year update from the randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial. J Hematol Oncol. 2017; 10(1):55.","DOI":"10.1186\/s13045-017-0417-z"},{"key":"28906","doi-asserted-by":"crossref","unstructured":"Cervantes F, Dupriez B, Passamonti F. Improving survival trends in primary myelofibrosis: an international study. J Clin Oncol. 2012; 30(24):2981-2987.","DOI":"10.1200\/JCO.2012.42.0240"},{"key":"28907","doi-asserted-by":"crossref","unstructured":"Chen DS, Mellman I.. Elements of cancer immunity and the cancer-immune set point. Nature. 2017; 541(7637):321-330.","DOI":"10.1038\/nature21349"},{"key":"28908","doi-asserted-by":"crossref","unstructured":"Boiocchi L, Espinal-Witter R, Geyer JT. Development of monocytosis in patients with primary myelofibrosis indicates an accelerated phase of the disease. 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Leukemia. 2019; 33(7):1570-1582.","DOI":"10.1038\/s41375-018-0360-1"}],"container-title":["Haematologica"],"original-title":[],"link":[{"URL":"https:\/\/haematologica.org\/article\/download\/9835\/71126","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/haematologica.org\/article\/download\/9835\/71127","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/haematologica.org\/article\/download\/9835\/73625","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/haematologica.org\/article\/download\/9835\/71126","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T09:57:48Z","timestamp":1794045468000},"score":1,"resource":{"primary":{"URL":"https:\/\/haematologica.org\/article\/view\/9835"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,30]]},"references-count":47,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9,1]]}},"URL":"https:\/\/doi.org\/10.3324\/haematol.2020.249441","relation":{},"ISSN":["1592-8721","0390-6078"],"issn-type":[{"value":"1592-8721","type":"electronic"},{"value":"0390-6078","type":"print"}],"subject":[],"published":{"date-parts":[[2020,7,30]]}}}