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Oncogenes, Fusion Genes And Tumor suppressor Genes

RETRACTED ARTICLE: Disruption of the Bcr-Abl/Hsp90 protein complex: a possible mechanism to inhibit Bcr-Abl-positive human leukemic blasts by novobiocin

Leukemia volume 22, pages 1402–1409 (2008)Cite this article

A Retraction to this article was published on 08 April 2020

Abstract

The Bcr-Abl fusion gene encodes for the p210Bcr-Abl or p185Bcr-Abl tyrosine kinase (TK) implicated in the pathogenesis of chronic myelogenous leukemia (CML) or acute lymphoblastic leukemia, respectively. Because Bcr-Abl TK is chaperoned by Hsp90 (90 kDa heat-shock protein), we investigated the effects of novobiocin (NB), an Hsp90 C-terminal inhibitor, on the viability of the Bcr-Abl-positive human leukemia cells HL-60/Bcr-Abl and K562, the expression of Bcr-Abl protein and the interaction between Hsp90 and Bcr-Abl TK. Present studies demonstrate that NB is a potent inhibitor of the growth of Bcr-Abl-positive human leukemia cells. NB induces cytosolic accumulation of cytochrome c and activation of caspase-9 and caspase-3, triggering apoptosis of HL-60/Bcr-Abl and K562 cells. Treatment of cell lines with NB disrupts Bcr-Abl /Hsp90 and Bcr-Abl /Hsp70 interactions, resulting in a decreased amount of intracellular Bcr-Abl protein levels. Co-treatment with the proteasome inhibitor N-acetyl leucyl-leucyl norlucinal increases NB-mediated accumulation of Bcr-Abl in the detergent-insoluble cellular fraction, which demonstrates that NB promotes proteasomal degradation of Bcr-Abl. Moreover, both imatinib-resistant K562/G01 and primary CML CD34+ cells are sensitive to NB.

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Acknowledgements

We thank Dr Kapil Bhalla for kindly providing the HL-60/Bcr-Abl cells and MD Xinjian Lin (University of California, San Diego) for acquiring and eventually distributing the HL-60/Bcr-Abl cells to us. We thank Professor Chunzheng Yang (Institute of Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China) for kindly providing the K562/G01 cell line. We also gratefully acknowledge the support of this project by the National Natural Science Foundation of China (30171158 and 30472187) and the Natural Science Foundation of the Fujian Province of China (C992001 and C0610025). This study was supported by grants from the National Natural Science Foundation of China (30171158 and 30472187) and the Natural Science Foundation of Fujian Province of China (C992001 and C0610025).

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Authors and Affiliations

  1. Deparment of Pharmacology, Institute of Clinical Pharmacology, Fujian Medical University, Fuzhou, PR China

    L X Wu, J H Xu, K Z Zhang, Q Lin, X W Huang & C X Wen

  2. Fujian Institute of Hematology, Union Hospital, Fujian Medical University, Fuzhou, PR China

    Y Z Chen

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Correspondence to J H Xu or Y Z Chen.

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The authors have retracted this article. An investigation by Fujian Medical University identified multiple errors in the assembly of the figures, most notably in the duplication of loading controls. All authors agree with this retraction.

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Wu, L., Xu, J., Zhang, K. et al. RETRACTED ARTICLE: Disruption of the Bcr-Abl/Hsp90 protein complex: a possible mechanism to inhibit Bcr-Abl-positive human leukemic blasts by novobiocin. Leukemia 22, 1402–1409 (2008). https://doi.org/10.1038/leu.2008.89

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