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Antileukaemia effect of rapamycin alone or in combination with daunorubicin on ph+ acute lymphoblastic leukaemia cell line

Authors

  • Xi Yang,

    1. Department of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, China
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  • Juan Lin,

    1. Department of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, China
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  • Yuping Gong,

    Corresponding author
    • Department of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, China
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  • Hongbing Ma,

    1. Department of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, China
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  • Xiao Shuai,

    1. Department of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, China
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  • Ruiqing Zhou,

    1. Department of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, China
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  • Yong Guo,

    1. Department of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, China
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  • Qingqing Shan,

    1. Department of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, China
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  • Guangcui He

    1. Department of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, China
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Yuping Gong, Department of Hematology, West China Hospital of Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan Province, China, 610041.

E-mail: gongyuping2010@yahoo.cn

Abstract

The translocation (9;22) (q34;q11), known as the Philadelphia (Ph) chromosome and bcr-abl fusion gene, is the common cytogenetic abnormality and an unfavourable prognosis in adult acute lymphoblastic leukaemia (ALL). Although chemotherapeutic treatment produced high rates of complete response in approximately 70%–80% of newly diagnosed Ph+ ALL, the onset of resistance and clinical relapse is rapid. Therefore, the efficacy of treatment in Ph+ ALL is still to be determined. In this study, we aimed to assess the antileukemic activity of rapamycin (RAPA) (Sigma-Aldrich Corporation, MO, USA), a mammalian target of rapamycin inhibitor, alone and in combination with daunorubicin (DNR) (Pharmacia & Upjohn Company, Germany) in a Ph+ acute lymphoblastic cell line SUP-B15 and a primary Ph+ ALL sample in vitro. Here, we demonstrated that 50 nmol/L of RAPA significantly intensified the inhibition induced by DNR on both Ph+ ALL cell line and a primary Ph+ ALL sample. Notably, we reported that the consequence of DNR treatment induced the over expression of the componets of mammalian target of rapamycin signalling pathway, whereas RAPA effectively eliminated this deleterious side effect of DNR, which might enhance DNR's ability to kill drug-resistant cancer. The synergistic effect was also associated with the increase in autophagy, blockage of cell cycle progression in the G1 phase. Altogether, our results suggest that DNR in combination with RAPA is more effective in the treatment of Ph+ ALL compared with DNR alone. Copyright © 2011 John Wiley & Sons, Ltd.

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