1.4 MiR-181a/b Significantly Enhance Drug Sensitivity of CLL Cells via Targeting Multiple Anti-Apoptosis Genes

Abstract

(P 0.5322) were not changed. 3. In this analysis, 4 patients carried p53 abnormality and 3 patients carried heterozygous ATM gene deletion. Levels of p21 in cytoplasm were not raised in CLL cells from patients with p53 abnormality following incubation with fludarabine. Elevation of p21 was detected in CLL cells that carried heterozygous ATM gene deletion, after fludarabine induction. 4. It appeared that apoptosis level (P 0.1704) and Puma expression level (P 0.5334) of CLL cells cultured in medium only were independent of p53 status, but apoptosis level (P 0.0109) and Puma expression level (P 0.0430) were upregulated by fludarabine in CLL cells with functional p53 to a greater extent than in CLL cells with dysfunctional p53. Fludarabine-induced apoptosis level (P 0.228) and Puma expression level (P 0.164) was similar in CLL cells with heterozygous ATM gene deletion than in p53 wild type CLL cells. 5. Fludarabine-induced apoptosis and the expression level of Puma seemed to be higher in CLL cells with mutated IGVH than those with ummutated IGVH, but the difference was not significant. Conclusion: Functional p53 was necessary for fludarabine-induced apoptosis. CLL cells with p53 gene deletion and/or p53 mutation showed dysfunction of p53. CLL cells with heterozygous ATM gene deletion carried functional p53. Fludarabine induced CLL cell apoptosis via activating p53 and then up-regulating its downstream effector Puma. Puma was the only essential factor for p53-mediated apoptosis, and Noxa and Bim seemed to play a more restricted role.