Open AccessMapping the CLEC 12A expression on myeloid progenitors in normal bone marrow; implications for understanding CLEC 12A‐related cancer stem cell biology
Author(s) -
Bill Marie,
B. van Kooten Niekerk Peter,
S. Woll Petter,
Laine Herborg Laura,
Stidsholt Roug Anne,
Hokland Peter,
Nederby Line
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13519
Subject(s) - myeloid , progenitor cell , haematopoiesis , biology , stem cell , cancer research , microbiology and biotechnology , immunology
The C‐type lectin domain family 12, member A ( CLEC 12A) 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 12A on the earliest stem‐ and myeloid progenitor subsets in normal bone marrow. We demonstrate distinct CLEC 12A expression in the classically defined myeloid progenitors, where on average 39.1% (95% CI [32.5;45.7]) of the common myeloid progenitors ( CMP s) expressed CLEC 12A, while for granulocyte‐macrophage progenitors and megakaryocyte‐erythroid progenitors ( MEP s), 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 CLEC 12A expression on MEP s, functional assessment of purified CLEC 12A +/− CMP s and MEP s in the colony‐forming unit assay demonstrated CLEC 12A + subsets to favour non‐erythroid colony growth. In conclusion, we provide evidence that the earliest CLEC 12A + cell in the haematopoietic tree is the classically defined CMP . Furthermore, we show that CLEC 12A‐expressing CMP s and MEP s are functionally different than their negative counterparts. Importantly, these data can help determine which cells will be spared during CLEC 12A‐targeted therapy, and we propose CLEC 12A to be included in future studies of myeloid cancer stem cell biology.