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BCR-ABL induces tyrosine phosphorylation of YAP leading to expression of Survivin and Cyclin D1 in chronic myeloid leukemia cells

International Journal of Hematology volume 110, pages 591–598 (2019)Cite this article

Abstract

In the present study, we studied downstream signals of BCR-ABL with regard to Src family kinases and YAP, a transcription cofactor and an effector of the Hippo pathway. We first checked the phosphorylation status of YAP and found that it was constitutively phosphorylated at tyrosine 357 in CML-derived cell lines (TCC-S and K562) but not in AML-derived cell lines (HL-60 and KG-1a). Treatment with imatinib or RK-20449 inhibited cell growth and decreased tyrosine phosphorylation of YAP in both CML lines. Expression of Survivin or Cyclin D1 was decreased in TCC-S, but not in either HL-60 or KG-1a. Furthermore, we established BCR-ABL stable transfectant and control empty vector transfectant from TF-1, a factor-dependent human erythroleukemia cell line, to verify our results obtained with CML cell lines. YAP was phosphorylated at Y357 constitutively in BCR-ABL stable transfectant but not in control transfectant, and treatment with imatinib or RK-20449, a Src family kinase-specific inhibitor, inhibited cell growth, YAP tyrosine phosphorylation, and expression of Cyclin D1 in BCR-ABL stable transfectant. These results suggest that BCR-ABL induces tyrosine phosphorylation of YAP presumably through Src family kinases, which results in expression of Survivin and Cyclin D leading to leukemogenesis in CML cells.

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Acknowledgements

We thank Dr. Xiaoyan Jiang (BC Cancer Agency—Terry Fox Laboratory) for MSCV-BCR-ABL-IRES-GFP, Dr. Yusuke Furukawa (Jichi University) for TCC-S, and Dr. Toshio Kitamura (University of Tokyo) for TF-1. We also thank our laboratory members, M.Sc. Konomi Maeda, M.Sc. Haruka Oshima, and Dr. Ryotaro Nishi for their collaborations.

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  1. Biomedical Sciences Course, Graduate School of Life Sciences, Ritsumeikan University, Noji-Higashi, Kusatsu, Shiga, 525-8577, Japan

    Kenta Moriyama & Toshiyuki Hori

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  1. Kenta Moriyama
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  2. Toshiyuki Hori
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Correspondence to Toshiyuki Hori.

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Moriyama, K., Hori, T. BCR-ABL induces tyrosine phosphorylation of YAP leading to expression of Survivin and Cyclin D1 in chronic myeloid leukemia cells. Int J Hematol 110, 591–598 (2019). https://doi.org/10.1007/s12185-019-02726-7

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  • DOI: https://doi.org/10.1007/s12185-019-02726-7

Keywords

  • Chronic myeloid leukemia
  • BCR-ABL
  • Src family kinase
  • Yes-associated protein
  • Tyrosine phosphorylation