Changes in gene expression induced by CDK9 inhibition alone and in combination with fludarabine

Using a transcriptomics approach we explored the mechanism(s) of synergy observed between CDKI-73 and fludarabine in primary CLL cells. The cytotoxic effects of CDKI-73 were associated with transcriptional inhibition of cdk9 target genes including MCL1 and XIAP. In contrast, fludarabine induced the transcription of these genes, an effect that was reversed by the combination of CDKI-73 and fludarabine. We used microarrays to explore the cytoxic synergy observed in primary CLL cells when we combined a novel CDK9 inhibitor with the purine nucleoside analogue fludarabine Primary CLL cells were inclubated with 0.1 μM CDKI-73, 10 μM fludarabine or the two drugs in combination for 4h.