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.
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Bill et al. (2018) studied this question.