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Bcl6 gene-silencing facilitates PMA-induced megakaryocyte differentiation in K562 cells

  • RESEARCH ARTICLE
  • Published:
Journal of Cell Communication and Signaling Aims and scope

Abstract

Targeted therapy via imatinib appears to be a promising approach for chronic myeloid leukemia (CML) therapy. However, refractory and resistance to imatinib therapy has encouraged many investigators to get involved in development of new therapeutic agents such as Phorbol 12-myrestrat 13-acetate (PMA) for patients with CML. In that line, we attempted to investigate the chemosensitizing effect of PMA on the imatinib-resistant cells. Based on our western blot analyses, resistant K562 cells (K562R) showed high levels of FoxO3a and Bcl6 expressions which were not modulated by imatinib treatment. However, upon PMA treatment, the levels of both FoxO3a and Bcl6 were up-regulated among both the sensitive and the resistant cells and this treatment was associated with initiation of megakaryocytic differentiation of the cells. SiRNA-silencing of FoxO3a led to augmentation of megakaryocytic differentiation of the cells. Similarly, siRNA gene silencing of Bcl6 enhanced the differentiation and induced cell apoptosis among both types of cells. Regarding these results, it might be concluded that Bcl6 knockdown combined with PMA therapy could present a new therapeutical strategy for refractory CML patients to imatinib.

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Abbreviations

CML:

chronic myeloid leukemia

PMA:

phorbol 12-myrestrat 13-acetate

Ph:

Philadelphia

TKIs:

tyrosine kinase inhibitors

DLCL:

diffuse large cell lymphoma

PKC:

protein kinase C

LICs:

leukemia-initiating cells

Tfh:

facilitates Follicular helper T

ALL:

acute lymphoblastic leukemia

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Acknowledgements

The authors appreciate the joint financial support of this investigation by the Research Council of University of Tehran and the University of Tehran Science and Technology Park.

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  1. Institute of Biochemistry and Biophysics, University of Tehran, P. O. Box, Tehran, 13145-1384, Iran

    Sedigheh Eskandari & Razieh Yazdanparast

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  1. Sedigheh Eskandari
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Correspondence to Razieh Yazdanparast.

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Eskandari, S., Yazdanparast, R. Bcl6 gene-silencing facilitates PMA-induced megakaryocyte differentiation in K562 cells. J. Cell Commun. Signal. 11, 357–367 (2017). https://doi.org/10.1007/s12079-017-0395-5

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