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Natural killer or natural killer/T cell lineage large granular lymphocytosis associated with dasatinib therapy for Philadelphia chromosome positive leukemia

¹ Chronic Myelogenous Leukemia Group, Department of Hematology/Medical Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
² Department of Pathology, University Health Network, University of Toronto, Toronto, Ontario, Canada
³ Department of Laboratory Hematology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
⁴ Department of Hematology/Medical Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
⁵ Department of Hematology/Oncology, Chonnam National University, Hwasun Hospital, Hwasun, Jeollanamdo, Korea

Correspondence: Dong Hwan (Dennis) Kim, M.D./Ph.D., Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Ilwon-dong 50, Kangnam-gu, Seoul, Korea, 1. E-mail:drkiim{at}medimail.co.kr

Dasatinib, a dual tyrosine kinase inhibitor, is known to modulate or suppress T-cell activation and proliferation. We report a series of 8 patients who developed chronic peripheral lymphocytosis, identified as natural killer cells or natural killer/T-cells based on their large granular lymphocyte morphologies and CD16^+, CD56⁺, CD3^– or CD3⁺ immunophenotypic profiles, out of 18 patients receiving dasatinib therapy. All cases that developed large granular lymphocyte lymphocytosis achieved optimal molecular response (8/8 in large granular lymphocyte⁺ patients vs. 3/10 in large granular lymphocyte^– patients, p=0.002). A ⁵¹Cr release assay demonstrated that natural killer cell cytotoxicity has been enhanced in a case of large granular lymphocyte lymphocytosis compared to normal healthy donors, and that natural killer cell cytotoxicity in dasatinib-responders was superior to that in non-responders. In summary, the present study suggests that natural killer or natural killer/T cell lineage large granular lymphocyte lymphocytosis develops in association with dasatinib therapy and that large granular lymphocyte might have a therapeutic effect on Ph⁺ leukemic cells.

Key words: lymphocytosis, large granular lymphocyte, natural killer cells, dasatinib.