{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T07:03:47Z","timestamp":1790492627241,"version":"4.1.0"},"reference-count":43,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"2","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2017,1,10]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> Immunologic surveillance of minimal residual disease in chronic myelogenous leukemia (CML) may be relevant for long-term control or cure of CML. Little is known about immune-modulatory effects of nilotinib in vivo, potentially predicting response to therapy. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> A prospective and comprehensive flow cytometry\u2013based immunomonitoring program paralleled the ENEST1st clinical study, investigating 52 nilotinib-na\u00efve patients with chronic-phase CML. Data were verified in independent validation cohorts. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> T cells of patients with CML at diagnosis expressed low l-selectin (CD62L) levels, which was not a result of proportional aberrations of T-cell subsets. Low numbers of CD62L-expressing CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells correlated with higher Sokal score, increased spleen size, and high leukocyte and peripheral-blood blast counts. At month 6 during nilotinib therapy, CD62L expression returned to levels of healthy individuals. The level of CD62L loss on T cells directly correlated with the extent of soluble CD62L (sCD62L) elevation. In parallel, the proteolytic activity of tumor necrosis factor \u03b1\u2013converting enzyme (TACE; ADAM17, CD156b), the metalloproteinase shedding CD62L, was increased at diagnosis and significantly decreased during nilotinib treatment. High CD62L<jats:sup>+<\/jats:sup> expression on both CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells and, vice versa, low sCD62L levels at CML diagnosis were linked to superior molecular responses. These findings were corroborated in independent validation cohorts. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> We demonstrate the prognostic impact of CD62L shedding from T cells and increased sCD62L plasma levels at CML diagnosis on molecular response to tyrosine kinase inhibitor therapy in early chronic-phase CML. Functionally, decreased CD62L may be a consequence of increased TACE-mediated CD62L cleavage and potentially impairs immune-cell function. Larger prospective studies are ongoing to confirm the prognostic relevance of this finding. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2016.67.0893","type":"journal-article","created":{"date-parts":[[2017,2,23]],"date-time":"2017-02-23T18:08:47Z","timestamp":1487873327000},"page":"175-184","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":35,"title":["Reduced CD62L Expression on T Cells and Increased Soluble CD62L Levels Predict Molecular Response to Tyrosine Kinase Inhibitor Therapy in Early Chronic-Phase Chronic Myelogenous Leukemia"],"prefix":"10.1200","volume":"35","author":[{"given":"Sieghart","family":"Sopper","sequence":"first","affiliation":[{"name":"Sieghart Sopper, G\u00fcnther Gastl, Matthias Baldauf, Zlatko Trajanoski, and Dominik Wolf, Medical University Innsbruck; Sieghart Sopper and Dominik Wolf, Tyrolean Cancer Research Institute; Matthias Baldauf, Oncotyrol, Innsbruck; Peter Valent, Medical University of Vienna, 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