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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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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. |
format | Online Article Text |
id | pubmed-5867061 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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