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MIP-1α/CCL3-mediated maintenance of leukemia-initiating cells in the initiation process of chronic myeloid leukemia

In the initiation process of chronic myeloid leukemia (CML), a small number of transformed leukemia-initiating cells (LICs) coexist with a large number of normal hematopoietic cells, gradually increasing thereafter and eventually predominating in the hematopoietic space. However, the interaction bet...

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Autores principales: Baba, Tomohisa, Naka, Kazuhito, Morishita, Soji, Komatsu, Norio, Hirao, Atsushi, Mukaida, Naofumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832924/
https://www.ncbi.nlm.nih.gov/pubmed/24166712
http://dx.doi.org/10.1084/jem.20130112
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author Baba, Tomohisa
Naka, Kazuhito
Morishita, Soji
Komatsu, Norio
Hirao, Atsushi
Mukaida, Naofumi
author_facet Baba, Tomohisa
Naka, Kazuhito
Morishita, Soji
Komatsu, Norio
Hirao, Atsushi
Mukaida, Naofumi
author_sort Baba, Tomohisa
collection PubMed
description In the initiation process of chronic myeloid leukemia (CML), a small number of transformed leukemia-initiating cells (LICs) coexist with a large number of normal hematopoietic cells, gradually increasing thereafter and eventually predominating in the hematopoietic space. However, the interaction between LICs and normal hematopoietic cells at the early phase has not been clearly delineated because of the lack of a suitable experimental model. In this study, we succeeded in causing a marked leukocytosis resembling CML from restricted foci of LICs in the normal hematopoietic system by direct transplantation of BCR-ABL gene–transduced LICs into the bone marrow (BM) cavity of nonirradiated mice. Herein, we observed that BCR-ABL(+)lineage(−)c-kit(−) immature leukemia cells produced high levels of an inflammatory chemokine, MIP-1α/CCL3, which promoted the development of CML. Conversely, ablation of the CCL3 gene in LICs dramatically inhibited the development of CML and concomitantly reduced recurrence after the cessation of a short-term tyrosine kinase inhibitor treatment. Finally, normal hematopoietic stem/progenitor cells can directly impede the maintenance of LICs in BM in the absence of CCL3 signal.
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spelling pubmed-38329242014-05-18 MIP-1α/CCL3-mediated maintenance of leukemia-initiating cells in the initiation process of chronic myeloid leukemia Baba, Tomohisa Naka, Kazuhito Morishita, Soji Komatsu, Norio Hirao, Atsushi Mukaida, Naofumi J Exp Med Article In the initiation process of chronic myeloid leukemia (CML), a small number of transformed leukemia-initiating cells (LICs) coexist with a large number of normal hematopoietic cells, gradually increasing thereafter and eventually predominating in the hematopoietic space. However, the interaction between LICs and normal hematopoietic cells at the early phase has not been clearly delineated because of the lack of a suitable experimental model. In this study, we succeeded in causing a marked leukocytosis resembling CML from restricted foci of LICs in the normal hematopoietic system by direct transplantation of BCR-ABL gene–transduced LICs into the bone marrow (BM) cavity of nonirradiated mice. Herein, we observed that BCR-ABL(+)lineage(−)c-kit(−) immature leukemia cells produced high levels of an inflammatory chemokine, MIP-1α/CCL3, which promoted the development of CML. Conversely, ablation of the CCL3 gene in LICs dramatically inhibited the development of CML and concomitantly reduced recurrence after the cessation of a short-term tyrosine kinase inhibitor treatment. Finally, normal hematopoietic stem/progenitor cells can directly impede the maintenance of LICs in BM in the absence of CCL3 signal. The Rockefeller University Press 2013-11-18 /pmc/articles/PMC3832924/ /pubmed/24166712 http://dx.doi.org/10.1084/jem.20130112 Text en © 2013 Baba et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Baba, Tomohisa
Naka, Kazuhito
Morishita, Soji
Komatsu, Norio
Hirao, Atsushi
Mukaida, Naofumi
MIP-1α/CCL3-mediated maintenance of leukemia-initiating cells in the initiation process of chronic myeloid leukemia
title MIP-1α/CCL3-mediated maintenance of leukemia-initiating cells in the initiation process of chronic myeloid leukemia
title_full MIP-1α/CCL3-mediated maintenance of leukemia-initiating cells in the initiation process of chronic myeloid leukemia
title_fullStr MIP-1α/CCL3-mediated maintenance of leukemia-initiating cells in the initiation process of chronic myeloid leukemia
title_full_unstemmed MIP-1α/CCL3-mediated maintenance of leukemia-initiating cells in the initiation process of chronic myeloid leukemia
title_short MIP-1α/CCL3-mediated maintenance of leukemia-initiating cells in the initiation process of chronic myeloid leukemia
title_sort mip-1α/ccl3-mediated maintenance of leukemia-initiating cells in the initiation process of chronic myeloid leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832924/
https://www.ncbi.nlm.nih.gov/pubmed/24166712
http://dx.doi.org/10.1084/jem.20130112
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