Abstract

Previously, we found a significant increase in TRAIL (TNFα-related apoptosis-inducing ligand) resistance of acute myeloid leukemia (AML) cells in multicellular aggregates in vitro that simulate the location of leukemia cells in the bone marrow. In this study, we tried to assess whether the increased resistance of the AML cells to the cytotoxic effect of TRAIL in multicellular aggregates in vitro can be associated with the launch of mechanisms mediated by cell differentiation or the acquisition of a pro-inflammatory phenotype. The phenotype of THP-1 cells in aggregated and disaggregated cultures was studied in comparison with the phenotype of a disaggregated THP-1 cell culture exposed to factors that induce monocyte-like differentiation or pro-inflammatory phenotype. It was found that an increase in the TRAIL resistance of the THP-1 cells in the aggregated culture was accompanied by the appearance of signs characteristic of monocyte-like differentiation and a pro-inflammatory phenotype. The results are of interest for developing approaches for suppressing TRAIL resistance of AML cells in human bone marrow.

中文翻译：

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急性髓样白血病细胞THP-1中分化和促炎表型的体征表现以及体外细胞聚集体中TRAIL抗性的增加

摘要

以前，我们发现模拟白血病细胞在骨髓中的多细胞聚集体中的急性髓细胞白血病（AML）细胞对TRAIL（TNFα相关的凋亡诱导配体）抵抗力显着增加。在这项研究中，我们试图评估AML细胞对TRAIL在体外多细胞聚集物中的细胞毒性作用的抗性增强是否与细胞分化介导的机制启动或促炎表型的获得有关。与暴露于诱导单核细胞样分化或促炎性表型的因素的分解THP-1细胞培养物的表型相比，研究了聚集和分解培养物中THP-1细胞的表型。发现在聚集培养物中THP-1细胞的TRAIL抗性的增加伴随出现单核细胞样分化和促炎表型的特征性体征。该结果对于开发用于抑制人骨髓中AML细胞的TRAIL抗性的方法是有意义的。