• Dong Hwan Kim, Suzanne Kamel-Reid, Hong Chang, Robert Sutherland, Chul Won Jung, Hyeoung-Joon Kim, Je-Jung Lee, and Jeffrey H Lipton.
• Chronic Myelogenous Leukemia Group, Department of Hematology/Medical Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada. drkiim@medimail.co.kr
• Haematologica. 2009 Jan 1; 94 (1): 135-9.

AbstractDasatinib, 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.

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