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

被引：126

作者：

Kim, Dong Hwan ^{[1
,2
]}

Kamel-Reid, Suzanne ^{[3
]}

Chang, Hong ^{[4
]}

Sutherland, Robert ^{[4
]}

Jung, Chul Won

Kim, Hyeoung-Joon ^{[5
]}

Lee, Je-Jung ^{[5
]}

Lipton, Jeffrey H. ^{[2
]}

机构：

[1] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med Hematol Oncol,Div Hemato Oncol, Seoul, South Korea

[2] Univ Toronto, Princess Margaret Hosp, Univ Hlth Network,Dept Hematol Med Oncol, Chron Myelogenous Leukemia Grp, Toronto, ON, Canada

[3] Univ Toronto, Dept Pathol, Univ Hlth Network, Toronto, ON, Canada

[4] Univ Toronto, Princess Margaret Hosp, Univ Hlth Network, Dept Haematol Lab, Toronto, ON, Canada

[5] Chonnam Natl Univ, Hwasun Hosp, Dept Hematol Oncol, Hwasun, Jeollanamdo, South Korea

来源：

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL | 2009年 / 94卷 / 01期

关键词：

lymphocytosis; large granular lymphocyte; natural killer cells; dasatinib; CHRONIC MYELOGENOUS LEUKEMIA; KINASE FYN; IMATINIB MESYLATE; TERM CULTURE; NK CELLS; ACTIVATION; PROLIFERATION; CYTOTOXICITY; MODULATION; EXPRESSION;

D O I：

10.3324/haematol.13151

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 Cr-51 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.

引用

页码：135 / 139

页数：5

共 22 条

[1] Regulation of natural cytotoxicity by the adaptor SAP and the Src-related kinase Fyn [J].