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 51 Cr 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.