TIM-3 as a novel therapeutic target for eradicating acute myelogenous leukemia stem cells

Acute myelogenous leukemia (AML) originates from self-renewing leukemic stem cells (LSCs), which represent the ultimate therapeutic target for AML. Recent studies have identified several AML LSC-specific surface antigens as candidate targets of therapeutic molecules. T cell immunoglobulin mucin-3 (T...

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Bibliographic Details
Published in:International journal of hematology 2013-12, Vol.98 (6), p.627-633
Main Authors: Kikushige, Yoshikane, Miyamoto, Toshihiro
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - pharmacology
Antibodies, Monoclonal - therapeutic use
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Hematology
Hematopoiesis - genetics
Hepatitis A Virus Cellular Receptor 2
Humans
Leukemia, Myeloid, Acute - drug therapy
Leukemia, Myeloid, Acute - metabolism
Medicine
Medicine & Public Health
Membrane Proteins - antagonists & inhibitors
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
Molecular Targeted Therapy
Neoplastic Stem Cells - drug effects
Neoplastic Stem Cells - metabolism
Oncology
Progress in Hematology
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Summary:Acute myelogenous leukemia (AML) originates from self-renewing leukemic stem cells (LSCs), which represent the ultimate therapeutic target for AML. Recent studies have identified several AML LSC-specific surface antigens as candidate targets of therapeutic molecules. T cell immunoglobulin mucin-3 (TIM-3) is expressed on LSCs in most types of AML, with the exception of acute promyelocytic leukemia, but not on normal hematopoietic stem cells (HSCs). In xenograft models reconstituted with human AML LSCs or HSCs, an anti-human TIM-3 mouse IgG2a antibody with cytotoxic activities eradicates AML LSCs in vivo, but does not affect normal human hematopoiesis. Thus, TIM-3 is a promising therapeutic target for the eradication of AML LSCs.
ISSN:0925-5710
1865-3774
DOI:10.1007/s12185-013-1433-6