人类红白血病K562细胞是慢性髓细胞白血病（CML）的典型细胞培养模型。这些细胞是假三倍体，并且带有费城染色体。因此，K562细胞被广泛用于研究BCR/ABL1癌基因和酪氨酸激酶抑制剂伊马替尼甲磺酸盐。此外，K562细胞过度表达转铁蛋白受体（TfR），已被用作通过受体介导的内吞作用以靶向细胞毒疗法的模型。在这里，我们对K562细胞进行了表征，重点关注细胞在长期培养中的核型、野生型（WT）和阿霉素耐药细胞中的TfR表达调节以及对组蛋白去乙酰化酶抑制剂（HDACi）的反应。核型分析表明K562细胞具有新的染色体，而基因表达分析则提示培养K562细胞与患者来源的白血病细胞有所偏移。我们通过免疫荧光和细胞表面受体结合放射分析证实了K562细胞上TfR的高表达。重要的是，高TfR表达也在患者来源的细胞中观察到，并且我们强调在阿霉素获得性耐药后TfR的持续表达。表观遗传学分析表明，在K562细胞中，启动子区域的允许性组蛋白乙酰化和甲基化调节了TfR的转录。最后，我们展示了K562细胞中HDAC酶的相对高表达，并且利用FDA批准的羟肟酸类化合物沃立尼斯坦展示了HDACi的化疗作用。通过形态学、红外光谱分析和代谢性质的检查，我们对K562细胞进行了全面的表征。总的来说，K562细胞培养系统一直被广泛用于研究CML的新疗法，尤其是在伊马替尼甲磺酸盐耐药的情况下显得尤为重要。©2023. Crown.

Human erythroleukemic K562 cells represent the prototypical cell culture model of chronic myeloid leukemia (CML). The cells are pseudo-triploid and positive for the Philadelphia chromosome. Therefore, K562 cells have been widely used for investigating the BCR/ABL1 oncogene and the tyrosine kinase inhibitor, imatinib-mesylate. Further, K562 cells overexpress transferrin receptors (TfR) and have been used as a model for targeting cytotoxic therapies, via receptor-mediated endocytosis. Here, we have characterized K562 cells focusing on the karyotype of cells in prolonged culture, regulation of expression of TfR in wildtype (WT) and doxorubicin-resistant cells, and responses to histone deacetylase inhibition (HDACi). Karyotype analysis indicates novel chromosomes and gene expression analysis suggests a shift of cultured K562 cells away from patient-derived leukemic cells. We confirm the high expression of TfR on K562 cells using immunofluorescence and cell-surface receptor binding radioassays. Importantly, high TfR expression is observed in patient-derived cells, and we highlight the persistent expression of TfR following doxorubicin acquired resistance. Epigenetic analysis indicates that permissive histone acetylation and methylation at the promoter region regulates the transcription of TfR in K562 cells. Finally, we show relatively high expression of HDAC enzymes in K562 cells and demonstrate the chemotoxic effects of HDACi, using the FDA-approved hydroxamic acid, vorinostat. Together with a description of morphology, infrared spectral analysis, and examination of metabolic properties, we provide a comprehensive characterization of K562 cells. Overall, K562 cell culture systems remain widely used for the investigation of novel therapeutics for CML, which is particularly important in cases of imatinib-mesylate resistance.© 2023. Crown.