Bendamustine alone or with rituximab modifies expression of apoptosis-regulating genes and proteins of CLL cells, depending on IGVH mutational status

Abstract

We studied whether bendamustine (BENDA) alone or with rituximab (RIT) modifies in vitro expression of apoptosis-involved genes and proteins of chronic lymphocytic leukemia (CLL) cells depending on IGVH mutational status. Circulating lymphocytes from 34 untreated patients (18 IGVH-MUT and 16 IGVH-UNMUT) were incubated with above drugs to evaluate proteins expression. Microarray analysis of 93 genes was performed in 14 patients. BENDA and BENDA + RIT increased expression of BAX and BBC3 in IGVH-MUT and IGVH-UNMUT groups, and significant differences in expression of above genes after BENDA + RIT were observed between both groups. Additionally, BENDA + RIT decreased NFκB and BCL-2 genes in IGVH-UNMUT patients and increased expression of P53, BAX and PUMA proteins in IGVH-MUT and UNMUT subjects. However, no significant differences were found between these groups. In conclusion, BENDA + RIT modified gene expression profile in CLL cells and affected expression of some apoptosis-regulating proteins in vitro. Expression of BAX and BBC3 depends on action of drugs and IGVH mutational status.

Keywords:

• Bendamustine
• rituximab
• chronic lymphocytic leukemia
• IGVH mutational status
• gene expression profile
• protein expression

Acknowledgements

The authors thank Dr A. Holub and Dr P. Jerzmanowski for their support in the enrollment of patients in the study. The authors also thank Edward Lowczowski for his help in preparing the English version of this manuscript.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2018.1493730.

Additional information

Funding

This work was supported by the Mundipharma Research Ltd (MRL), UK [grant number 508/1-093-01/508-01-088] and the Medical University of Lodz [grant number 503/1-093-01/503-11-004].