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

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.