title: Natural killer or natural killer/T cell lineage large granular lymphocytosis associated with dasatinib therapy for Philadelphia chromosome positive leukemia.
abstract: 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.
authors.affiliation: 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
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Kim
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
authors.forename: Hong
authors.initials: H
authors.lastname: Chang
authors.forename: Robert
authors.initials: R
authors.lastname: Sutherland
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Jung
authors.forename: Hyeoung-Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Je-Jung
authors.initials: JJ
authors.lastname: Lee
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Lipton
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D013844:Thiazoles; D000069439:Dasatinib