Cyclin dependent kinases (Cdks) not only drive cell cycle progression, but also control transcription. For example, Cdk7 and Cdk9 phosphorylate specific sites on the C-terminal domain of RNA polymerase II (pol II) to promote transcription initiation and elongation. Our previous experience with flavopiridol, a non-selective pan-Cdk inhibitor, in primary chronic lymphocytic leukemia (CLL) cells demonstrated inhibition of RNA pol II-driven mRNA synthesis, reduction of the expression of short lived anti-apoptotic proteins, and induction of apoptosis in CLL cells in vitro (
Disclosure:Employment: Ute Hoch, Rachael E. Hawtin and Judith A. Fox are employees of Sunesis Pharmaceuticals. Research Funding: William G. Wierda and William Plunkett are recipients of research grants from Sunesis Pharceuticals.