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BMS-777607 promotes megakaryocytic differentiation and induces polyploidization in the CHRF-288-11 cells

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Abstract

Introduction of a polyploidy inducer is a promising strategy to achieve a high level of polyploidization during megakaryocytic (MK) differentiation. Here, we report that a multi-kinase inhibitor, BMS-777607, is a potent polyploidy inducer for elevating high ploidy cell formation in the MK-differentiated CHRF-288-11 (CHRF) cells. Our result showed that BMS-777607 strongly inhibited cell division without affecting cell viability when detected at day 1 after treatment. As a consequence, the high ploidy (≥8N) cells were accumulated in culture for 8 days, with an increase from 16.2 to 75.2 % of the total cell population. The elevated polyploidization was accompanied by the increased expression level of MK marker, CD41 (platelet glycoprotein IIb/IIIa, GPIIb/IIIa), suggesting that BMS-777607 promoted both polyploidization and commitment of MK-differentiated CHRF cells. Platelet-like fragments (PFs) were released by mature CHRF cells. Based on a flow cytometry assay, it was found that the PFs produced from BMS-777607-treated cells tended to have larger size and higher expression of GPIIb/IIIa, a receptor for platelet adhesion. Taken together, these results suggested that BMS-777607 promoted MK differentiation of CHRF cells and increased the functional property of platelet-like fragments.

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Acknowledgments

This research was in part supported by Grant-in-Aids for Scientific Researches, No. 25289295, from the Ministry of Education, Culture, Sports, Science and Technology of Japan. We thank Prof. William M. Miller of Northwestern University for kindly providing CHRF-288-11 and K562 cells.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Chemical Engineering, Department of Materials Engineering Science, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama-cho, Toyonaka, Osaka, 560-8531, Japan

    Retno Wahyu Nurhayati, Yoshihiro Ojima & Masahito Taya

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  1. Retno Wahyu Nurhayati
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  2. Yoshihiro Ojima
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  3. Masahito Taya
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Correspondence to Masahito Taya.

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Nurhayati, R.W., Ojima, Y. & Taya, M. BMS-777607 promotes megakaryocytic differentiation and induces polyploidization in the CHRF-288-11 cells. Human Cell 28, 65–72 (2015). https://doi.org/10.1007/s13577-014-0102-2

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  • DOI: https://doi.org/10.1007/s13577-014-0102-2

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