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首页> 外文期刊>Journal of cellular and molecular medicine. >Mapping the CLEC12A expression on myeloid progenitors in normal bone marrow; implications for understanding CLEC12A‐related cancer stem cell biology
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Mapping the CLEC12A expression on myeloid progenitors in normal bone marrow; implications for understanding CLEC12A‐related cancer stem cell biology

机译：在正常骨髓中映射CLEC12A表达骨髓祖细胞;了解Clec12A相关癌症干细胞生物学的影响

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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.
机译：C型凝集素结构域系列12，成员A（CLEC12A）受体已成为骨髓恶性肿瘤中的白血病相关和癌症干细胞标志物。然而，缺乏详细描述其在正常血上的表达缺乏。在这里，我们已经表征了正常骨髓中最早的茎和骨髓祖亚群的Clec12a的表达模式。我们在经典定义的骨髓祖祖培养器中展示了明显的Clec12a表达，平均39.1％（95％Ci [32.5; 45.7]）的常见骨髓祖细胞（CMP）表达CLEC12A，而对于粒细胞 - 巨噬细胞祖细胞和巨核细胞 - 红细胞祖细胞（ MEP），平均百分比为81.0％（95％CI [76.0; 85.9]）和11.9％（95％CI [9.3; 14.6]）。符合MEP的降低的CLEC12A表达，纯化的CLEC12A的功能评估 + /α-α和meps在菌落形成单元测定中显示CLEC12A + 子集，以支持非 - 红细胞殖民地生长。总之，我们提供了证据表明，血液树中最早的CLEC12A + 单元是经典定义的CMP。此外，我们表明CLEC12A表达的CMP和MEPS在功能上与它们的负对值不同。重要的是，这些数据可以有助于确定在CLEC12A靶向治疗期间将抑制哪些细胞，并且我们提出CLEC12A被列入骨髓癌干细胞生物学的未来研究。

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