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BLM helicase is activated in BCR/ABL leukemia cells to modulate responses to cisplatin

Oncogene volume 24, pages 3914–3922 (2005)Cite this article

Abstract

Bloom protein (BLM) is a 3′–5′ helicase, mutated in Bloom syndrome, which plays an important role in response to DNA double-strand breaks and stalled replication forks. Here, we show that BCR/ABL tyrosine kinase, which also modulates DNA repair capacity, is associated with elevated expression of BLM. Downregulation of BLM by antisense cDNA or dominant-negative mutant inhibits homologous recombination repair (HRR) and increases sensitivity to cisplatin in BCR/ABL-positive cells. Bone marrow cells from mice heterozygous for BLM mutation, BLMCin/+, transfected with BCR/ABL display increased sensitivity to cisplatin compared to those obtained from the wild-type littermates. BCR/ABL promotes interactions of BLM with RAD51, while simultaneous overexpression of BLM and RAD51 in normal cells increases drug resistance. These data suggest that BLM collaborates with RAD51 to facilitate HRR and promotes the resistance of BCR/ABL-positive leukemia cells to DNA-damaging agents.

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Acknowledgements

This work was supported by NIH RO1 CA 89052 (TS), NIH UOI CA 84291 (JG), American Cancer Society Grant RSG-98-348-04-LIB (TS) and New Investigator Grant from Leukemia Research Foundation (AS). TS is a Scholar of the Leukemia and Lymphoma Society. JG is an Investigator with the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, 19122, USA

    Artur Slupianek, Ewa Gurdek, Mateusz Koptyra, Michal O Nowicki, Khwaja M Siddiqui & Tomasz Skorski

  2. Howard Hughes Medical Institute and Department of Molecular Genetics, Biochemistry, and Microbiology, The University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA

    Joanna Groden

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  1. Artur Slupianek
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Correspondence to Artur Slupianek or Tomasz Skorski.

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Slupianek, A., Gurdek, E., Koptyra, M. et al. BLM helicase is activated in BCR/ABL leukemia cells to modulate responses to cisplatin. Oncogene 24, 3914–3922 (2005). https://doi.org/10.1038/sj.onc.1208545

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