化疗耐药是急性髓系白血病（AML）治疗失败的主要原因，也是其死亡的主要原因。替托泊苷是一种DNA拓扑异构酶-II抑制剂，单独应用或与阿糖胞苷、氮杂胞苷、长春碱类和蒽环类联合应用用于复发/难治性AML的治疗。本研究旨在利用HL60细胞株确定和了解AML内替托泊苷耐药机制。HL60细胞经过不断增量的替托泊苷处理后，通过在半固体培养基中培养耐药细胞，分离出耐药类群落。选择了三个耐替托泊苷系列分别为HL60-EtopR H1A、HL60-EtopR H1B和HL60-EtopR H1C的克隆，这些克隆较与亲本细胞相比对替托泊苷表现出4.78、2.39和4.42倍的耐药性。为了确定替托泊苷耐药HL60-EtopR细胞与亲本细胞之间的分子差异，进行了基于微阵列的基因表达谱分析。我们发现，替托泊苷耐药细胞中的SRC酪氨酸激酶家族成员基因表达上调。需要进一步研究以评估Src抑制剂在靶向替托泊苷耐药细胞中的作用。© 2022生物医学信息学。

Chemotherapy resistance is the main reason for treatment failure in acute myeloid leukemia (AML) and the major cause of its mortality. Etoposide is a DNA topoisomerase-II inhibitor that is used either as a single agent or in combination with cytarabine, azacytidine, vinca alkaloids, and anthracyclines for the treatment of relapsed /refractory AML. In this study, we sought to determine and understand the mechanism of etoposide resistance in AML using the HL60 cell line.HL60 cells were treated with incremental doses of etoposide and resistant colonies were isolated by culturing the resistant cells in semi-solid culture media. Three clones were selected for etoposide resistance namely, HL60-EtopR H1A, HL60-EtopR H1B, and HL60-EtopR H1C which demonstrated 4.78, 2.39, and 4.42-fold higher resistance to etoposide compared with the parental cells. To determine molecular differences between the etoposide-resistant HL60-EtopR cells and the parental cells, microarray-based gene expression profiling was performed. We found up regulation of members of the src tyrosine kinase family genes in the etoposide resistant cells. Further studies are required to evaluate the role of Src inhibitors in targeting etoposide resistant cells.© 2022 Biomedical Informatics.