Jaguścik Aleksandra B, Ziółkowska Ewelina I, Wołowiec Dariusz, Zawlik Izabela, Soin Michał, Jarych Dariusz, Robak Tadeusz, Korycka-Wołowiec Anna B
Department of Hematology Medical University of Lodz, Poland.
Clinical Department of Hematology, Cell Therapies and Internal Diseases, Wroclaw Medical University, Poland.
Adv Clin Exp Med. 2025 Jun;34(6):973-985. doi: 10.17219/acem/199382.
Venetoclax (VEN) and cladribine (2-CdA) are active agents in the treatment of chronic lymphocytic leukemia (CLL), although their precise pro-apoptotic mechanisms in CLL cells remain unclear. However, in vitro studies suggest that these drugs may alter the expression of several proteins involved in apoptosis.
The aim of the study was to evaluate the effect of VEN and 2-CdA, used individually and in combination, on the expression of apoptosis-related genes in CLL cells in vitro.
Mononuclear cells were collected from peripheral blood of 40 previously untreated CLL patients. The expression of 17 apoptosis-related genes was assessed using nCounter NanoString technology before and after 48-h in vitro incubation with VEN, 2-CdA or their combination (VEN + 2-CdA).
Venetoclax + 2-CdA had a stronger effect on all tested genes except BCL2 and PMAIP compared to VEN alone, and on BID, BIK, FADD, P53, and SMAD3 compared to 2-CdA alone.
Venetoclax and 2-CdA may exert their pro-apoptotic effects on CLL cells in vitro, at least in part, by stimulating the expression of several apoptosis-related genes. The antileukemic activity of VEN is further enhanced when combined with 2-CdA.
维奈克拉（VEN）和克拉屈滨（2-CdA）是治疗慢性淋巴细胞白血病（CLL）的有效药物，尽管它们在CLL细胞中确切的促凋亡机制仍不清楚。然而，体外研究表明，这些药物可能会改变几种参与凋亡的蛋白质的表达。
本研究旨在评估VEN和2-CdA单独及联合使用对体外CLL细胞中凋亡相关基因表达的影响。
从40例未经治疗的CLL患者外周血中收集单核细胞。在与VEN、2-CdA或其组合（VEN + 2-CdA）进行48小时体外孵育之前和之后，使用nCounter NanoString技术评估17个凋亡相关基因的表达。
与单独使用VEN相比，维奈克拉+ 2-CdA对除BCL2和PMAIP之外的所有测试基因有更强的作用，与单独使用2-CdA相比，对BID、BIK、FADD、P53和SMAD3有更强的作用。
维奈克拉和2-CdA可能至少部分地通过刺激几种凋亡相关基因的表达，在体外对CLL细胞发挥促凋亡作用。与2-CdA联合使用时，VEN的抗白血病活性进一步增强。
