{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:34:47Z","timestamp":1791178487055,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2010,7,21]],"date-time":"2010-07-21T00:00:00Z","timestamp":1279670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2010,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tyrosine kinase inhibitors (TKIs) are the current standard treatment in chronic myeloid leukemia (CML). In addition to the BCR\u2010ABL target oncoprotein, they also inhibit off\u2010target kinases (e.g. c\u2010KIT, TEC, SRC), some of which have physiological functions in immune responses. <jats:italic>In vitro<\/jats:italic> studies have implied immunosuppressive effects of TKI treatment. As comprehensive <jats:italic>in vivo<\/jats:italic> data are missing, we aimed at analyzing the detailed immunoprofile of patients with CML at diagnosis and during therapy. We collected 88 peripheral blood (PB) and 73 bone marrow (BM) samples from 54 patients with CML at diagnosis, during imatinib and dasatinib therapies. Leukocytes and lymphocyte subclasses were analyzed with an extensive flow cytometry panel including markers for activation, differentiation and memory status. At diagnosis, a lower proportion of B cells and dendritic cells and an increased amount of NKT\u2010like cells were detected in the BM. During imatinib therapy, all these changes normalized and the immunoprofile resembled healthy controls. However, dasatinib patients were clearly divided into two distinct groups: one similar to healthy controls and the other showing immunoactivation characterized by significant elevations of CD8+, NK\u2010 and NKT\u2010like cells in PB. T cells of the latter group strongly expressed CD57+, HLA\u2010DR and CD45RO and had low CD62L antigen levels characteristic of late memory cytotoxic lymphocytes. Our results indicate that while both TKIs show immunosuppressive effects <jats:italic>in vitro<\/jats:italic>, they have a significant and differential effect on the numbers and proportions of immune effector cells <jats:italic>in vivo<\/jats:italic>. In particular, in a distinct subgroup of dasatinib\u2010treated patients, immune reactivity is markedly enhanced warranting careful follow\u2010up.<\/jats:p>","DOI":"10.1111\/j.1600-0609.2010.01501.x","type":"journal-article","created":{"date-parts":[[2010,7,21]],"date-time":"2010-07-21T20:11:59Z","timestamp":1279743119000},"page":"387-398","source":"Crossref","is-referenced-by-count":82,"title":["Immunoprofiling of patients with chronic myeloid leukemia at diagnosis and during tyrosine kinase inhibitor therapy"],"prefix":"10.1111","volume":"85","author":[{"given":"Peter","family":"Rohon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimmo","family":"Porkka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satu","family":"Mustjoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,7,21]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa062867"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-03-080689"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.84"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-07-102061"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-03-011239"},{"key":"e_1_2_8_7_2","doi-asserted-by":"crossref","DOI":"10.1182\/blood.V112.11.187.187","article-title":"Is It Possible to Stop Imatinib in Patients with Chronic Myeloid Leukemia? An Update from a French Pilot Study and First Results from the Multicentre \u00ab Stop Imatinib \u00bb (STIM) Study","volume":"112","author":"Mahon FX","year":"2008","journal-title":"Blood"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404807"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-3807"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4393"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2008.02.006"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-04-084814"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00234.x"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0952-7915(94)90115-5"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-02-138701"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.13151"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.46"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2009.02206.x"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.273"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)70931-4"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404858"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(08)00408-9"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401146"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-2126(97)00152-5"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-01-0150"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-12-256800"},{"key":"e_1_2_8_27_2","first-page":"3986","article-title":"Roles of CD4+CD25(high) FOXP3+ Tregs in lymphomas and tumors are complex","volume":"13","author":"Ke X","year":"2008","journal-title":"Front Biosci"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-04-151969"},{"key":"e_1_2_8_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2009.05.012"}],"container-title":["European Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1600-0609.2010.01501.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1600-0609.2010.01501.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T22:31:54Z","timestamp":1697322714000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1600-0609.2010.01501.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,7,21]]},"references-count":28,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2010,11]]}},"alternative-id":["10.1111\/j.1600-0609.2010.01501.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1600-0609.2010.01501.x","archive":["Portico"],"relation":{},"ISSN":["0902-4441","1600-0609"],"issn-type":[{"value":"0902-4441","type":"print"},{"value":"1600-0609","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,7,21]]}}}