International Journal of Hematology

DOI: 10.1007/s12185-019-02726-7 Pages: 591-598

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

1. Ritsumeikan University, Biomedical Sciences Course, Graduate School of Life Sciences

Correspondence to:
Toshiyuki Hori
Email: toshihor@sk.ritsumei.ac.jp

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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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