Abstract |
Dasatinib, a 2nd-generation tyrosine kinase inhibitor (TKI), can specifically induce large granular lymphocytes (LGL) in some patients with Philadelphia chromosome (Ph)-positive leukemia. To investigate the properties of the induced LGLs, we performed prospective and longitudinal analyses. From Feb 2011 to Jan 2013, a total of 17 patients with Ph-positive leukemia who were previously untreated or refractory to imatinib were enrolled. T cell receptor (TCR)-γ/δ gene rearrangements and phenotypic profiles of lymphocytes were examined before and during administration of dasatinib. LGL lymphocytosis was observed in half of the dasatinib-treated cases (LGL+ group), showing a relation to increased achievement of complete cytogenetic response within 6 months. The phenotypes of the increased lymphocytes were revealed to be mostly natural killer cells. In the LGL+ group, clonal TCR-γ gene rearrangements were frequently detected at diagnosis (six of nine cases) and persisted during therapy, compared with only two of eight in the LGL- group. The proportion of regulatory T cells to CD4+ T cells at diagnosis was lower in the LGL+ compared with the LGL- group (median 4.2 vs. 6.6 %), and this disparity was sustained throughout the therapeutic period. These results demonstrate that immunological condition at diagnosis may affect LGL lymphocytosis in some dasatinib-treated patients.
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Authors | Yuji Shimura, Shigeo Horiike, Yasuhiko Tsutsumi, Mayumi Hatsuse, Akira Okano, Shin-Ichi Fuchida, Tsutomu Kobayashi, Yosuke Matsumoto, Junya Kuroda, Eri Kawata-Iida, Hitoji Uchiyama, Nobuhiko Uoshima, Chihiro Shimazaki, Hiroto Kaneko, Yutaka Kobayashi, Masafumi Taniwaki |
Journal | International journal of hematology
(Int J Hematol)
Vol. 102
Issue 4
Pg. 426-33
(Oct 2015)
ISSN: 1865-3774 [Electronic] Japan |
PMID | 26267232
(Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Receptors, Antigen, T-Cell, gamma-delta
- Dasatinib
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Topics |
- Adult
- Aged
- CD4-Positive T-Lymphocytes
- Dasatinib
(administration & dosage)
- Female
- Follow-Up Studies
- Gene Rearrangement, delta-Chain T-Cell Antigen Receptor
- Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor
- Humans
- Killer Cells, Natural
(metabolism)
- Leukemia, Large Granular Lymphocytic
(blood, drug therapy, genetics)
- Male
- Middle Aged
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
(blood, drug therapy, genetics)
- Receptors, Antigen, T-Cell, gamma-delta
(blood, genetics)
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