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Int J Hematol. 2018 Dec;108(6):588-597. doi: 10.1007/s12185-018-2517-0. Epub 2018 Aug 27.

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

Author information

1
Department of Hematology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
2
Department of Hematology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. ttakaku@juntendo.ac.jp.
3
Division of Cell Biology, Biomedical Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
4
Department of Biofunctional Microbiota, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
5
Department of Hematology, Juntendo Shizuoka Hospital, Shizuoka, Japan.
6
Department of Hematology, Juntendo Urayasu Hospital, Chiba, Japan.
7
Department of Hematology, Juntendo Nerima Hospital, Tokyo, Japan.
8
Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.

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.

KEYWORDS:

CD57 expression; Chronic myelogenous leukemia; Cytotoxic CD4+ T cell; Dasatinib; Large granular lymphocyte

PMID:
30151740
DOI:
10.1007/s12185-018-2517-0
[Indexed for MEDLINE]

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