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

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Clinical and Experimental Medicine Pub Date : 2025-05-28 DOI:10.17219/acem/199382

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

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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.

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在体外实验中，Venetoclax单独使用或与cladribine联合使用可改变慢性淋巴细胞白血病细胞凋亡调节基因的表达。

背景：Venetoclax （VEN）和cladribine （2-CdA）是治疗慢性淋巴细胞白血病（CLL）的活性药物，尽管它们在CLL细胞中促凋亡的确切机制尚不清楚。然而，体外研究表明，这些药物可能会改变一些参与细胞凋亡的蛋白质的表达。目的：研究VEN和2-CdA单独或联合使用对体外CLL细胞凋亡相关基因表达的影响。材料和方法：收集40例未经治疗的CLL患者外周血单个核细胞。采用nCounter NanoString技术检测17个细胞凋亡相关基因在VEN、2-CdA或两者联合（VEN + 2-CdA）体外培养48 h前后的表达情况。结果：与单独使用VEN相比，Venetoclax + 2-CdA对除BCL2和PMAIP外的所有测试基因都有更强的影响，对BID、BIK、FADD、P53和SMAD3也比单独使用2-CdA有更强的影响。结论：Venetoclax和2-CdA可能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联用后，VEN的抗白血病活性进一步增强。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advances in Clinical and Experimental Medicine MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

3.70

自引率

4.80%

发文量

153

审稿时长

6-12 weeks

期刊介绍： Advances in Clinical and Experimental Medicine has been published by the Wroclaw Medical University since 1992. Establishing the medical journal was the idea of Prof. Bogumił Halawa, Chair of the Department of Cardiology, and was fully supported by the Rector of Wroclaw Medical University, Prof. Zbigniew Knapik. Prof. Halawa was also the first editor-in-chief, between 1992-1997. The journal, then entitled "Postępy Medycyny Klinicznej i Doświadczalnej", appeared quarterly. Prof. Leszek Paradowski was editor-in-chief from 1997-1999. In 1998 he initiated alterations in the profile and cover design of the journal which were accepted by the Editorial Board. The title was changed to Advances in Clinical and Experimental Medicine. Articles in English were welcomed. A number of outstanding representatives of medical science from Poland and abroad were invited to participate in the newly established International Editorial Staff. Prof. Antonina Harłozińska-Szmyrka was editor-in-chief in years 2000-2005, in years 2006-2007 once again prof. Leszek Paradowski and prof. Maria Podolak-Dawidziak was editor-in-chief in years 2008-2016. Since 2017 the editor-in chief is prof. Maciej Bagłaj. Since July 2005, original papers have been published only in English. Case reports are no longer accepted. The manuscripts are reviewed by two independent reviewers and a statistical reviewer, and English texts are proofread by a native speaker. The journal has been indexed in several databases: Scopus, Ulrich’sTM International Periodicals Directory, Index Copernicus and since 2007 in Thomson Reuters databases: Science Citation Index Expanded i Journal Citation Reports/Science Edition. In 2010 the journal obtained Impact Factor which is now 1.179 pts. Articles published in the journal are worth 15 points among Polish journals according to the Polish Committee for Scientific Research and 169.43 points according to the Index Copernicus. Since November 7, 2012, Advances in Clinical and Experimental Medicine has been indexed and included in National Library of Medicine’s MEDLINE database. English abstracts printed in the journal are included and searchable using PubMed http://www.ncbi.nlm.nih.gov/pubmed.