The BH3-only protein Puma plays an essential role in p53-mediated apoptosis of chronic lymphocytic leukemia cells

Abstract

The purpose of this study was to explore the characteristics and functions of BH3-only proteins Puma, Noxa and Bim in the prognosis, therapy and drug resistance of chronic lymphocytic leukemia (CLL). Puma, Noxa and Bim mRNAs were evaluated by real-time quantitative reverse transcriptase-polymerase chain reaction, and correlations between their expression levels and CLL prognostic markers were analyzed. Primary CLL samples were treated in vitro with fludarabine to investigate the role of Puma, Noxa and Bim in the response to chemotherapeutic drugs which act through activation of the p53 pathway. We found that a low expression level of Puma was associated with some markers of poor prognosis. However, the level of Noxa or Bim was not different in patients with CLL with variant clinical features and prognostic factors. Puma expression was up-regulated after fludarabine treatment in primary CLL cells, but there was no significant difference for Noxa and Bim. Up-regulation of Puma occurred only in CLL cells with functional p53. CLL cells with p53 abnormalities were deficient in the activation of Puma by chemotherapeutics. These results suggest that a lack of Puma induction may contribute to the development of resistance to anticancer agents in CLL.

Keywords::

• Chronic lymphocytic leukemia
• BH3-only protein
• Puma
• Noxa
• Bim

Potential conflict of interest:

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This study was supported by the National Natural Science Foundation of China (30971296, 81170485, 81170488, 81200360), Natural Science Foundation of Jiangsu Province (BK2010584, BK2012484), Key Project of the Health Department of Jiangsu Province (K201108), Jiangsu Province's Medical Elite Program (RC2011169), Project Funded by Priority Academic Program Development of Jiangsu Higher Education Institute (JX10231801), National Public Health Grand Research Foundation (201202017), Program for Development of the Innovative Research Team in the First Affiliated Hospital of NJMU, Key Project supported by the Medical Science and Technology Development Foundation of Nanjing Department of Health (ZKX09016) and Project for State Key Clinical Department Construction.