title: Megakaryocytic differentiation in human chronic myelogenous leukemia K562 cells induced by ionizing radiation in combination with phorbol 12-myristate 13-acetate.
abstract: 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.
authors.affiliation: Department of Radiology and Radiation Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Hirose
authors.forename: Satoru
authors.initials: S
authors.lastname: Monzen
authors.forename: Haruka
authors.initials: H
authors.lastname: Sato
authors.forename: Mariko
authors.initials: M
authors.lastname: Sato
authors.forename: Masahiko
authors.initials: M
authors.lastname: Aoki
authors.forename: Yoshiomi
authors.initials: Y
authors.lastname: Hatayama
authors.forename: Hideo
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Narita
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takai
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kashiwakura
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects*; D006801:Humans; D020014:K562 Cells; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000528:radiation effects*; D008533:Megakaryocytes / Q000378:metabolism* / Q000473:pathology* / Q000528:radiation effects; D011829:Radiation Dosage; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage*
chemical_list: D017382:Reactive Oxygen Species; D013755:Tetradecanoylphorbol Acetate