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TIM‐3 in normal and malignant hematopoiesis: Structure, function, and signaling pathways

Acute myeloid leukemia (AML) is hierarchically organized by self‐renewing leukemic stem cells (LSCs). LSCs originate from hematopoietic stem cells (HSCs) by acquiring multistep leukemogenic events. To specifically eradicate LSCs, while keeping normal HSCs intact, the discrimination of LSCs from HSCs...

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Autor principal: Kikushige, Yoshikane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409405/
https://www.ncbi.nlm.nih.gov/pubmed/34159709
http://dx.doi.org/10.1111/cas.15042
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author Kikushige, Yoshikane
author_facet Kikushige, Yoshikane
author_sort Kikushige, Yoshikane
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description Acute myeloid leukemia (AML) is hierarchically organized by self‐renewing leukemic stem cells (LSCs). LSCs originate from hematopoietic stem cells (HSCs) by acquiring multistep leukemogenic events. To specifically eradicate LSCs, while keeping normal HSCs intact, the discrimination of LSCs from HSCs is important. We have identified T‐cell immunoglobulin and mucin‐domain containing‐3 (TIM‐3) as an LSC‐specific surface molecule in human myeloid malignancies and demonstrated its essential function in maintaining the self‐renewal ability of LSCs. TIM‐3 has been intensively investigated as a “coinhibitory” or “immune checkpoint” molecule of T cells. However, little is known about its distinct function in T cells and myeloid malignancies. In this review, we discuss the structure of TIM‐3 and its function in normal blood cells and LSCs, emphasizing the specific signaling pathways involved, as well as the therapeutic applications of TIM‐3 molecules in human myeloid malignancies.
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spelling pubmed-84094052021-09-03 TIM‐3 in normal and malignant hematopoiesis: Structure, function, and signaling pathways Kikushige, Yoshikane Cancer Sci Review Articles Acute myeloid leukemia (AML) is hierarchically organized by self‐renewing leukemic stem cells (LSCs). LSCs originate from hematopoietic stem cells (HSCs) by acquiring multistep leukemogenic events. To specifically eradicate LSCs, while keeping normal HSCs intact, the discrimination of LSCs from HSCs is important. We have identified T‐cell immunoglobulin and mucin‐domain containing‐3 (TIM‐3) as an LSC‐specific surface molecule in human myeloid malignancies and demonstrated its essential function in maintaining the self‐renewal ability of LSCs. TIM‐3 has been intensively investigated as a “coinhibitory” or “immune checkpoint” molecule of T cells. However, little is known about its distinct function in T cells and myeloid malignancies. In this review, we discuss the structure of TIM‐3 and its function in normal blood cells and LSCs, emphasizing the specific signaling pathways involved, as well as the therapeutic applications of TIM‐3 molecules in human myeloid malignancies. John Wiley and Sons Inc. 2021-07-14 2021-09 /pmc/articles/PMC8409405/ /pubmed/34159709 http://dx.doi.org/10.1111/cas.15042 Text en © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Review Articles
Kikushige, Yoshikane
TIM‐3 in normal and malignant hematopoiesis: Structure, function, and signaling pathways
title TIM‐3 in normal and malignant hematopoiesis: Structure, function, and signaling pathways
title_full TIM‐3 in normal and malignant hematopoiesis: Structure, function, and signaling pathways
title_fullStr TIM‐3 in normal and malignant hematopoiesis: Structure, function, and signaling pathways
title_full_unstemmed TIM‐3 in normal and malignant hematopoiesis: Structure, function, and signaling pathways
title_short TIM‐3 in normal and malignant hematopoiesis: Structure, function, and signaling pathways
title_sort tim‐3 in normal and malignant hematopoiesis: structure, function, and signaling pathways
topic Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409405/
https://www.ncbi.nlm.nih.gov/pubmed/34159709
http://dx.doi.org/10.1111/cas.15042
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