Dinaciclib synergizes with BH3 mimetics targeting BCL-2 and BCL-X_L in multiple myeloma cell lines partially dependent on MCL-1 and in plasma cells from patients.

ABSTRACT: A better understanding of multiple myeloma (MM) biology has led to the development of novel therapies. However, MM is still an incurable disease and new pharmacological strategies are needed. Dinaciclib, a multiple cyclin-dependent kinase (CDK) inhibitor, which inhibits CDK1, 2, 5 and 9, displays significant antimyeloma activity as found in phase II clinical trials. In this study, we have explored the mechanism of dinaciclib-induced death and evaluated its enhancement by different BH3 mimetics in MM cell lines as well as in plasma cells from MM patients. Our results indicate a synergistic effect of dinaciclib-based combinations with B-cell lymphoma 2 or B-cell lymphoma extra-large inhibitors, especially in MM cell lines with partial dependence on myeloid cell leukemia sequence 1 (MCL-1). S

SUBMITTER: Beltran-Visiedo M 

PROVIDER: S-EPMC10701777 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature