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Eskandari S, Yazdanparast R. Bcl6 gene-silencing facilitates PMA-induced megakaryocyte differentiation in K562 cells. J Cell Commun Signal. 2017;11(4):357-367doi: 10.1007/s12079-017-0395-5.
Eskandari, S., & Yazdanparast, R. (2017). Bcl6 gene-silencing facilitates PMA-induced megakaryocyte differentiation in K562 cells. Journal of cell communication and signaling, 11(4), 357-367. https://doi.org/10.1007/s12079-017-0395-5
Eskandari, Sedigheh, and Yazdanparast, Razieh. "Bcl6 gene-silencing facilitates PMA-induced megakaryocyte differentiation in K562 cells." Journal of cell communication and signaling vol. 11,4 (2017): 357-367. doi: https://doi.org/10.1007/s12079-017-0395-5
Eskandari S, Yazdanparast R. Bcl6 gene-silencing facilitates PMA-induced megakaryocyte differentiation in K562 cells. J Cell Commun Signal. 2017 Dec;11(4):357-367. doi: 10.1007/s12079-017-0395-5. Epub 2017 Jun 06. PMID: 28589317; PMCID: PMC5704040.
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J Cell Commun Signal. 2017 Dec;11(4):357-367. doi: 10.1007/s12079-017-0395-5. Epub 2017 Jun 06.

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

Journal of cell communication and signaling

Sedigheh Eskandari, Razieh Yazdanparast

Affiliations

  1. Institute of Biochemistry and Biophysics, University of Tehran, P. O. Box, Tehran, 13145-1384, Iran.
  2. Institute of Biochemistry and Biophysics, University of Tehran, P. O. Box, Tehran, 13145-1384, Iran. [email protected].

PMID: 28589317 PMCID: PMC5704040 DOI: 10.1007/s12079-017-0395-5

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.

Keywords: Bcl6; Differentiation; FoxO3a; Imatinib; K562

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