Journal Article

Megakaryocytic differentiation in human chronic myelogenous leukemia K562 cells induced by ionizing radiation in combination with phorbol 12-myristate 13-acetate

Katsumi Hirose, Satoru Monzen, Haruka Sato, Mariko Sato, Masahiko Aoki, Yoshiomi Hatayama, Hideo Kawaguchi, Yuichiro Narita, Yoshihiro Takai and Ikuo Kashiwakura

in Journal of Radiation Research

Published on behalf of Japan Radiation Research Society and Japanese Society for Therapeutic Radiology and Oncology

Volume 54, issue 3, pages 438-446
Published in print May 2013 | ISSN: 0449-3060
Published online December 2012 | e-ISSN: 1349-9157 | DOI:

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Differentiation-induction therapy is an attractive approach in leukemia treatment. It has been suggested that the accumulation of intracellular reactive oxygen species (ROS) is involved in megakaryocytic differentiation induced by phorbol 12-myristate 13-acetate (PMA) in the K562 leukemia cell line. Therefore, a ROS-inducible technique could be a powerful method of differentiation induction. Accordingly, we hypothesized that ionizing radiation contributes to the acceleration of megakaryocytic differentiation through the accumulation of intracellular ROS in leukemia cells. In the present study, ionizing radiation was shown to promote PMA-induced megakaryocytic differentiation. Cells with high CD41 expression sustained intracellular ROS levels effectively. The enhancement of differentiation by ionizing radiation was found to be regulated through the mitogen-activated protein kinase (MAPK) pathway, involving both extracellular signal-regulated protein kinase 1/2 (ERK1/2) and p38 MAPK. Ionizing radiation also controlled mRNA expression of the oxidative stress response gene heme oxygenase-1 (HO1). Consequently, we concluded that intracellular ROS, increased by ionizing radiation, modulate megakaryocytic differentiation downstream of the MAPK pathway.

Keywords: K562 cells; megakaryocytopoiesis; ROS; MAPK

Journal Article.  3915 words.  Illustrated.

Subjects: Radiology ; Nuclear Chemistry, Photochemistry, and Radiation

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