Natural killer or natural killer/T cell lineage large granular lymphocytosis associated with dasatinib therapy for Philadelphia chromosome positive leukemia.
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.
Kim
Dong Hwan
DH
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
Kamel-Reid
Suzanne
S
Chang
Hong
H
Sutherland
Robert
R
Jung
Chul Won
CW
Kim
Hyeoung-Joon
HJ
Lee
Je-Jung
JJ
Lipton
Jeffrey H
JH
D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D019070:Cell Lineage / Q000187:drug effects* / Q000276:immunology; D000069439:Dasatinib; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008218:Lymphocytosis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D055611:Natural Killer T-Cells / Q000187:drug effects* / Q000276:immunology; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use; D013844:Thiazoles / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011743:Pyrimidines; D013844:Thiazoles; D000069439:Dasatinib