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Mapping the CLEC12A expression on myeloid progenitors in normal bone marrow; implications for understanding CLEC12A‐related cancer stem cell biology

The C‐type lectin domain family 12, member A (CLEC12A) receptor has emerged as a leukaemia‐associated and cancer stem cell marker in myeloid malignancies. However, a detailed delineation of its expression in normal haematopoiesis is lacking. Here, we have characterized the expression pattern of CLEC...

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Autores principales: Bill, Marie, B. van Kooten Niekerk, Peter, S. Woll, Petter, Laine Herborg, Laura, Stidsholt Roug, Anne, Hokland, Peter, Nederby, Line
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867061/
https://www.ncbi.nlm.nih.gov/pubmed/29411522
http://dx.doi.org/10.1111/jcmm.13519
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author Bill, Marie
B. van Kooten Niekerk, Peter
S. Woll, Petter
Laine Herborg, Laura
Stidsholt Roug, Anne
Hokland, Peter
Nederby, Line
author_facet Bill, Marie
B. van Kooten Niekerk, Peter
S. Woll, Petter
Laine Herborg, Laura
Stidsholt Roug, Anne
Hokland, Peter
Nederby, Line
author_sort Bill, Marie
collection PubMed
description The C‐type lectin domain family 12, member A (CLEC12A) receptor has emerged as a leukaemia‐associated and cancer stem cell marker in myeloid malignancies. However, a detailed delineation of its expression in normal haematopoiesis is lacking. Here, we have characterized the expression pattern of CLEC12A on the earliest stem‐ and myeloid progenitor subsets in normal bone marrow. We demonstrate distinct CLEC12A expression in the classically defined myeloid progenitors, where on average 39.1% (95% CI [32.5;45.7]) of the common myeloid progenitors (CMPs) expressed CLEC12A, while for granulocyte‐macrophage progenitors and megakaryocyte‐erythroid progenitors (MEPs), the average percentages were 81.0% (95% CI [76.0;85.9]) and 11.9% (95% CI [9.3;14.6]), respectively. In line with the reduced CLEC12A expression on MEPs, functional assessment of purified CLEC12A(+/−) CMPs and MEPs in the colony‐forming unit assay demonstrated CLEC12A(+) subsets to favour non‐erythroid colony growth. In conclusion, we provide evidence that the earliest CLEC12A(+) cell in the haematopoietic tree is the classically defined CMP. Furthermore, we show that CLEC12A‐expressing CMPs and MEPs are functionally different than their negative counterparts. Importantly, these data can help determine which cells will be spared during CLEC12A‐targeted therapy, and we propose CLEC12A to be included in future studies of myeloid cancer stem cell biology.
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spelling pubmed-58670612018-04-01 Mapping the CLEC12A expression on myeloid progenitors in normal bone marrow; implications for understanding CLEC12A‐related cancer stem cell biology Bill, Marie B. van Kooten Niekerk, Peter S. Woll, Petter Laine Herborg, Laura Stidsholt Roug, Anne Hokland, Peter Nederby, Line J Cell Mol Med Original Articles The C‐type lectin domain family 12, member A (CLEC12A) receptor has emerged as a leukaemia‐associated and cancer stem cell marker in myeloid malignancies. However, a detailed delineation of its expression in normal haematopoiesis is lacking. Here, we have characterized the expression pattern of CLEC12A on the earliest stem‐ and myeloid progenitor subsets in normal bone marrow. We demonstrate distinct CLEC12A expression in the classically defined myeloid progenitors, where on average 39.1% (95% CI [32.5;45.7]) of the common myeloid progenitors (CMPs) expressed CLEC12A, while for granulocyte‐macrophage progenitors and megakaryocyte‐erythroid progenitors (MEPs), the average percentages were 81.0% (95% CI [76.0;85.9]) and 11.9% (95% CI [9.3;14.6]), respectively. In line with the reduced CLEC12A expression on MEPs, functional assessment of purified CLEC12A(+/−) CMPs and MEPs in the colony‐forming unit assay demonstrated CLEC12A(+) subsets to favour non‐erythroid colony growth. In conclusion, we provide evidence that the earliest CLEC12A(+) cell in the haematopoietic tree is the classically defined CMP. Furthermore, we show that CLEC12A‐expressing CMPs and MEPs are functionally different than their negative counterparts. Importantly, these data can help determine which cells will be spared during CLEC12A‐targeted therapy, and we propose CLEC12A to be included in future studies of myeloid cancer stem cell biology. John Wiley and Sons Inc. 2018-02-07 2018-04 /pmc/articles/PMC5867061/ /pubmed/29411522 http://dx.doi.org/10.1111/jcmm.13519 Text en © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Bill, Marie
B. van Kooten Niekerk, Peter
S. Woll, Petter
Laine Herborg, Laura
Stidsholt Roug, Anne
Hokland, Peter
Nederby, Line
Mapping the CLEC12A expression on myeloid progenitors in normal bone marrow; implications for understanding CLEC12A‐related cancer stem cell biology
title Mapping the CLEC12A expression on myeloid progenitors in normal bone marrow; implications for understanding CLEC12A‐related cancer stem cell biology
title_full Mapping the CLEC12A expression on myeloid progenitors in normal bone marrow; implications for understanding CLEC12A‐related cancer stem cell biology
title_fullStr Mapping the CLEC12A expression on myeloid progenitors in normal bone marrow; implications for understanding CLEC12A‐related cancer stem cell biology
title_full_unstemmed Mapping the CLEC12A expression on myeloid progenitors in normal bone marrow; implications for understanding CLEC12A‐related cancer stem cell biology
title_short Mapping the CLEC12A expression on myeloid progenitors in normal bone marrow; implications for understanding CLEC12A‐related cancer stem cell biology
title_sort mapping the clec12a expression on myeloid progenitors in normal bone marrow; implications for understanding clec12a‐related cancer stem cell biology
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867061/
https://www.ncbi.nlm.nih.gov/pubmed/29411522
http://dx.doi.org/10.1111/jcmm.13519
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