Tari Kaveh, Nasimian Ahmad, Kazi Julhash U, Abroun Saied
Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden.
Int J Mol Cell Med. 2023;12(3):229-241. doi: 10.22088/IJMCM.BUMS.12.3.229.
Venetoclax, a specific inhibitor of the BCL2 protein, is administered for the treatment of acute lymphoblastic leukemia. However, despite being utilized in conjunction with chemotherapy, the drug exhibits instances of resistance. The exact mechanisms responsible for this resistance remain relatively obscure. Within the context of this investigation, the study aimed to explore the involvement of anti- and pro-apoptotic proteins as one of the potential mechanisms underlying this resistance phenomenon. Blast cells were extracted from patients diagnosed with B&T acute lymphoid leukemia. Subsequently, these cells were subjected to a cultivation process. Following the cultivation, treatment with the Venetoclax drug was administered to both groups of B&T cells. Additionally, one group from each cell type was designated as a control. The relative expression levels of genes , , and were assessed in comparison to the control group. Annexin V-fluorescein isothiocyanate and propidium iodide staining was done to check cell apoptosis. The results showed a significant increase in the expression of BIM gene and a significant decrease in gene compared to the control group, but the change in the expression of gene was not significant. Also, an increase in apoptosis was observed in the treatment groups compared to the control. Although it was shown that changes in the expression of pro- and anti-apoptotic genes can lead to an increase in cell apoptosis and a decrease in the number of blast cells, more studies are needed to investigate the simultaneous effect of Venetoclax drug with other drugs and also in the form of a clinical trial.
维奈托克是一种BCL2蛋白的特异性抑制剂，用于治疗急性淋巴细胞白血病。然而，尽管它与化疗联合使用，但该药物仍存在耐药情况。导致这种耐药的确切机制仍相对不明。在本研究中，该研究旨在探索抗凋亡蛋白和促凋亡蛋白作为这种耐药现象潜在机制之一的作用。从被诊断为B&T急性淋巴细胞白血病的患者中提取原始细胞。随后，对这些细胞进行培养。培养后，对两组B&T细胞都用维奈托克药物进行治疗。此外，每种细胞类型中的一组被指定为对照组。与对照组相比，评估了基因、和的相对表达水平。进行膜联蛋白V-异硫氰酸荧光素和碘化丙啶染色以检查细胞凋亡。结果显示，与对照组相比，BIM基因的表达显著增加，基因的表达显著降低，但基因表达的变化不显著。此外，与对照组相比，治疗组的细胞凋亡增加。尽管已表明促凋亡基因和抗凋亡基因的表达变化可导致细胞凋亡增加和原始细胞数量减少，但仍需要更多研究来调查维奈托克药物与其他药物同时使用的效果以及进行临床试验。
