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

研究成果: ジャーナルへの寄稿学術誌査読

366 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)708-717
ページ数10
ジャーナルCell stem cell
7
6
DOI
出版ステータス出版済み - 12月 3 2010

!!!All Science Journal Classification (ASJC) codes

  • 分子医療
  • 遺伝学
  • 細胞生物学

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