International Journal of Hematology

DOI: 10.1007/s12185-018-2517-0 Pages: 1-10

Dasatinib-induced anti-leukemia cellular immunity through a novel subset of CD57 positive helper/cytotoxic CD4 T cells in chronic myelogenous leukemia patients

1. Juntendo University School of Medicine, Department of Hematology

2. Juntendo University, Division of Cell Biology, Biomedical Research Center, Graduate School of Medicine

3. Juntendo University, Department of Biofunctional Microbiota, Graduate School of Medicine

4. Juntendo Shizuoka Hospital, Department of Hematology

5. Juntendo Urayasu Hospital, Department of Hematology

6. Juntendo Nerima Hospital, Department of Hematology

7. Ehime University, Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine

Correspondence to:
Tomoiku Takaku
Tel: 81(3)3813-3111
Email: ttakaku@juntendo.ac.jp

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Abstract

Dasatinib induces lymphocytosis of large granular lymphocytes (LGLs) in a proportion of patients with chronic myelogenous leukemia (CML), and is associated with better clinical outcomes. LGLs consist of cytotoxic T lymphocytes and natural killer cells; however, the context and phenotypic/functional features of each type of LGL are unknown. To better define features of these LGLs, we investigated lymphocytosis in CML patients treated with dasatinib. D57-positive and CD4-positive type I T-helper (Th) cells (CD57+ Th cells) rarely occur in CML patients without lymphocytosis and in healthy individuals; however, a substantial increase in the proportion of CD57+ Th cells was observed in CML patients treated with dasatinib. In addition, these cells showed appreciable levels of cytocidal activity via cytotoxic degranulation. Analysis of T-cell receptor α and β sequences showed a skewed T-cell repertoire in the CD57+ Th cells. Furthermore, patients with LGLs and CD57+ Th lymphocytosis achieved stronger molecular responses than did those without lymphocytosis. While further studies are warranted, our observations suggest that dasatinib induces the expansion of CD57+ Th-LGLs, which may play a crucial role in the dasatinib-induced response against Philadelphia chromosome-positive leukemia.

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