Flavopiridol: Where do we stand in chronic lymphocytic leukemia?

While the exact temporal and casual relationships among the various pathways leading to reversal of the antiapoptotic state and induction of cell death in B-CLL remain to be full defined, it is clear from this paper and other reports that flavopiridol exerts its antitumor activity in B-CLL by inducing apoptosis. Flavopiridol activates caspase-3, by the downregulation of NO synthase and/or other mechanism(s), distal or p53. Its ability to induce apoptosis in p53-independent manner makes this drug of great interest in B-CLL, given the importance of P53 mutations and deletions in the progression and drug resistance of this disease. Preclinical and clinical studies are being conducted to identify the optimal dosing schedule of this agent in B-CLL, and further clinical investigation is warranted. In addition, laboratory studies indicate that flavopiridol's eventual role B-CLL may be in combination chemotheraphy regimes. Thus, while this paper and other studies have shed considerable light on this promising clinical drug require further study.