TIM-3 as a therapeutic target for malignant stem cells in acute myelogenous leukemia.
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.
Department of Medicine and Biosystemic Sciences, Kyushu University Graduate School of Medicine, Fukuoka, Japan.
Yoshikane
Y
Kikushige
Koichi
K
Akashi
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D006410:Hematopoiesis; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D014411:Neoplastic Stem Cells / Q000276:immunology* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins