ホンダ　ヒロアキ   Honda Hiroaki   本田　浩章    所属   研究施設 研究施設    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Paradoxical counteraction by imatinib against cell death in myeloid progenitor 32D cells expressing p210BCR-ABL.
掲載誌名	正式名：Oncotarget 略　 称：Oncotarget ISSNコード：19492553/19492553
掲載区分	国外
巻・号・頁	9(60),pp.31682-31696
著者・共著者	TAKITA Morichika†, TSUKAHARA Fujiko†, MISHIMA Taishi, IEGUCHI Katsuaki, YAMADA Masayuki, HONDA Hiroaki, MARU Yoshiro*
発行年月	2018/08/03
概要	Chronic myeloid leukemia (CML) is believed to be caused by the tyrosine kinase p210BCR-ABL, which exhibits growth-promoting and anti-apoptotic activities. However, mechanisms that allow cell differentiation in CML still remain elusive. Here we established tetracycline (Tet)-regulatable p210BCR-ABL-expressing murine 32D myeloid progenitor (32D/TetOff-p210) cells to explore p210BCR-ABL-induced cell death and differentiation. Tet-regulatable overexpression of p210BCR-ABL induced cell death due to the activation of both caspase-1 and caspase-3, coincident with the differentiation from myeloid progenitors into CD11b+Ly6C+Ly6G+ cells with segmented nuclei, exemplified as granulocytic myeloid-derived suppressor cells (G-MDSC), and the ability to secrete IL-1β, TNF-α, and S100A8/A9 into the culture supernatant. Treatment with imatinib almost completely abrogated all these phenotypes. Moreover, overexpression of a sensor of activated caspase-1 based on fluorescence resonance energy transfer (FRET) probe enabled us to detect activation of caspase-1 in a human CML cell line, K562. Furthermore, increased numbers of splenic G-MDSC associated with enhancement of S100A8/A9 production were observed in transgenic mice expressing p210BCR-ABL compared with that in wild-type mice. We also propose the novel mode of cell death in this 32D/TetOff-p210 system termed as myeloptosis.
DOI	10.18632/oncotarget.25849
PMID	30167087