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TIM‐3 as a therapeutic target for malignant stem cells in acute myelogenous leukemia
Author(s) -
Kikushige Yoshikane,
Akashi Koichi
Publication year - 2012
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2012.06550.x
Subject(s) - haematopoiesis , stem cell , myeloid leukemia , acute promyelocytic leukemia , leukemia , immunology , cancer research , antibody , biology , antigen , cytotoxic t cell , medicine , in vitro , cell culture , microbiology and biotechnology , retinoic acid , biochemistry , genetics
Acute myeloid leukemia (AML) originates from self‐renewing leukemic stem cells (LSCs), an ultimate therapeutic target for AML. Recent studies have shown that many AML LSC–specific surface antigens could be such candidates. T cell immunoglobulin mucin‐3 (TIM‐3) is expressed on LSCs in most types of AML, except for acute promyelocytic leukemia, but not on normal hematopoietic stem cells (HSCs). In mouse models reconstituted with human AML LSCs or human hematopoietic stem cells, a human TIM‐3 mouse IgG2a antibody with complement‐dependent and antibody‐dependent cellular cytotoxic activities eradicates AML LSCs in vivo but does not affect normal human hematopoiesis. Thus, TIM‐3 is one of the promising targets to eradicate AML LSCs.