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本田 浩章
Department Research Institutes and Facilities, Research Institutes and Facilities Position Professor |
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| Article types | Original article |
| Language | English |
| Peer review | Peer reviewed |
| Title | Paradoxical counteraction by imatinib against cell death in myeloid progenitor 32D cells expressing p210BCR-ABL. |
| Journal | Formal name：Oncotarget Abbreviation：Oncotarget ISSN code：19492553/19492553 |
| Domestic / Foregin | Foregin |
| Volume, Issue, Page | 9(60),pp.31682-31696 |
| Author and coauthor | TAKITA Morichika†, TSUKAHARA Fujiko†, MISHIMA Taishi, IEGUCHI Katsuaki, YAMADA Masayuki, HONDA Hiroaki, MARU Yoshiro* |
| Publication date | 2018/08/03 |
| Summary | 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 |