TY - JOUR
T1 - TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells
AU - Kikushige, Yoshikane
AU - Shima, Takahiro
AU - Takayanagi, Shin Ichiro
AU - Urata, Shingo
AU - Miyamoto, Toshihiro
AU - Iwasaki, Hiromi
AU - Takenaka, Katsuto
AU - Teshima, Takanori
AU - Tanaka, Toshiyuki
AU - Inagaki, Yoshimasa
AU - Akashi, Koichi
N1 - Funding Information:
This work was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology in Japan. S.-i.T. and Y.I. are employees of Kyowa Hakko Kirin Co., Ltd.
PY - 2010/12/3
Y1 - 2010/12/3
N2 - 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.
AB - 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.
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U2 - 10.1016/j.stem.2010.11.014
DO - 10.1016/j.stem.2010.11.014
M3 - Article
C2 - 21112565
AN - SCOPUS:78649686241
SN - 1934-5909
VL - 7
SP - 708
EP - 717
JO - Cell stem cell
JF - Cell stem cell
IS - 6
ER -