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首页> 美国卫生研究院文献>The Journal of Clinical Investigation >Relationship between HLA-DR expression by normal myeloid progenitor cells and inhibition of colony growth by prostaglandin E. Implications for prostaglandin E resistance in chronic myeloid leukemia.
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Relationship between HLA-DR expression by normal myeloid progenitor cells and inhibition of colony growth by prostaglandin E. Implications for prostaglandin E resistance in chronic myeloid leukemia.

机译：正常髓样祖细胞表达HLA-DR与前列腺素E抑制菌落生长之间的关系。对慢性粒细胞白血病前列腺素E耐药性的影响。

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The expression of HLA-DR antigens by normal myeloid progenitor cells (CFU-GM) has been linked to inhibition of colony growth by prostaglandin E (PGE), while resistance to the inhibitory effects of PGE in chronic myeloid leukemia (CML) has been attributed to a lower fraction of HLA-DR+ CFU-GM in this disease. However, we have previously shown that virtually all CFU-GM in normal bone marrow (NBM) as well as CML peripheral blood express HLA-DR antigens, which raises the possibility that these surface molecules may not be the sole determinants of a progenitor cell's sensitivity to PGE. In order to evaluate the relationship between HLA-DR expression and prostaglandin inhibition, we partially purified NBM progenitor cells using fluorescence-activated cell sorting to prepare cell fractions with high and low HLA-DR antigen density. Normal progenitor cells with high DR density tended to form monocyte colonies in agar culture, whereas the low DR density fraction was enriched for granulocyte colony-forming cells. Inhibition by PGE was greatest in the high DR+ fraction and was largely restricted to monocyte progenitor cells. Inhibition of CFU-GM by PGE was less in CML than in NBM, but this decreased inhibition correlated with a significantly lower number of monocyte-CFU in CML. These data suggest that high HLA-DR antigen density may select for normal progenitor cells that are committed to monocyte differentiation and are, therefore, more likely to be inhibited by PGE. The relative deficit of monocyte progenitor cells in CML may partially explain the phenomenon of PGE resistance in this disease.
机译：正常骨髓祖细胞（CFU-GM）的HLA-DR抗原表达与前列腺素E（PGE）抑制菌落生长有关，而对慢性粒细胞白血病（CML）抑制PGE抑制作用的作用已被归因于在这种疾病中HLA-DR + CFU-GM的含量较低。但是，我们先前已经证明，正常骨髓（NBM）和CML外周血中几乎所有CFU-GM都表达HLA-DR抗原，这增加了这些表面分子可能不是祖细胞敏感性的唯一决定因素的可能性。到PGE。为了评估HLA-DR表达与前列腺素抑制之间的关系，我们使用荧光激活细胞分选法部分纯化了NBM祖细胞，以制备具有高低HLA-DR抗原密度的细胞级分。具有高DR密度的正常祖细胞在琼脂培养中倾向于形成单核细胞集落，而具有低DR密度的部分则富集粒细胞集落形成细胞。在高DR +分数中，PGE的抑制作用最大，并且很大程度上局限于单核细胞祖细胞。在CML中，PGE对CFU-GM的抑制作用要小于NBM，但这种抑制作用的降低与CML中单核细胞-CFU的数目显着降低有关。这些数据表明，高HLA-DR抗原密度可以选择致力于单核细胞分化的正常祖细胞，因此更有可能被PGE抑制。 CML中单核祖细胞的相对缺乏可能部分解释了该疾病中PGE耐药的现象。

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