Published online 9 December 2008
Haematologica, Vol 94, Issue 1, 135-139 doi:10.3324/haematol.13151
Copyright © 2009 by Ferrata Storti Foundation
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Lymphoproliferative Disorders

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

Dong Hwan Kim1,4, Suzanne Kamel-Reid2, Hong Chang3, Robert Sutherland3, Chul Won Jung4, Hyeoung-Joon Kim5, Je-Jung Lee5, Jeffrey H. Lipton1

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.




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R. Zambello and G. Semenzato
Large granular lymphocyte disorders: new etiopathogenetic clues as a rationale for innovative therapeutic approaches
Haematologica, October 1, 2009; 94(10): 1341 - 1345.
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