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维奈托克单独使用或与克拉屈滨联合使用时，可在体外改变慢性淋巴细胞白血病细胞中凋亡调节基因的表达。

Venetoclax used alone, or in combination with cladribine, changes the expression of apoptosis-regulating genes in chronic lymphocytic leukemia cells in vitro.

作者信息

Jaguścik Aleksandra B, Ziółkowska Ewelina I, Wołowiec Dariusz, Zawlik Izabela, Soin Michał, Jarych Dariusz, Robak Tadeusz, Korycka-Wołowiec Anna B

机构信息

Department of Hematology Medical University of Lodz, Poland.

Clinical Department of Hematology, Cell Therapies and Internal Diseases, Wroclaw Medical University, Poland.

出版信息

Adv Clin Exp Med. 2025 Jun;34(6):973-985. doi: 10.17219/acem/199382.

DOI:10.17219/acem/199382

PMID:40432340

Abstract

BACKGROUND

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.

OBJECTIVES

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.

MATERIAL AND METHODS

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).

RESULTS

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.

CONCLUSIONS

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.

摘要