TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells

Yoshikane Kikushige, Takahiro Shima, Shin Ichiro Takayanagi, Shingo Urata, Toshihiro Miyamoto, Hiromi Iwasaki, Katsuto Takenaka, Takanori Teshima, Toshiyuki Tanaka, Yoshimasa Inagaki, Koichi Akashi

Research output: Contribution to journalArticle

194 Citations (Scopus)

Abstract

Acute myeloid leukemia (AML) originates from self-renewing leukemic stem cells (LSCs), an ultimate therapeutic target for AML. Here we identified T cell immunoglobulin mucin-3 (TIM-3) as a surface molecule expressed on LSCs in most types of AML except for acute promyelocytic leukemia, but not on normal hematopoietic stem cells (HSCs). TIM-3+ but not TIM-3- AML cells reconstituted human AML in immunodeficient mice, suggesting that the TIM-3+ population contains most, if not all, of functional LSCs. We established an anti-human TIM-3 mouse IgG2a antibody having complement-dependent and antibody-dependent cellular cytotoxic activities. This antibody did not harm reconstitution of normal human HSCs, but blocked engraftment of AML after xenotransplantation. Furthermore, when it is administered into mice grafted with human AML, this treatment dramatically diminished their leukemic burden and eliminated LSCs capable of reconstituting human AML in secondary recipients. These data suggest that TIM-3 is one of the promising targets to eradicate AML LSCs.

Original languageEnglish
Pages (from-to)708-717
Number of pages10
JournalCell stem cell
Volume7
Issue number6
DOIs
Publication statusPublished - Dec 3 2010

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Cell Biology

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