Study of the mechanism of apoptosis and drug resistance in leukemic cells
| Project/Area Number |
15591112
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
TASHIRO Satoshi Hiroshima University, Research Institute for Radiation Biology and Medicine, Professor, 原爆放射線医科学研究所, 教授 (20243610)
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| Co-Investigator(Kenkyū-buntansha) |
IGARASHI Kazuhiko Hiroshima University, Graduate School of Biomedical Science, Professor, 大学院・医歯薬学総合研究科, 教授 (00250738)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | CML / Bach2 / PML / imatinib / ABL / PML / STI571 / Abl遺伝子 / Rad51 |
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| Research Abstract |
Imatinib is a molecular targeting drug against chronic myelocytic leukemia (CML), and induces apoptosis of leukemic cells. Bach2, a B cell specific transcription factor and a proapoptotic factor, is upregulated by imatinib in CML. To study the mechanism of the induction of apoptosis by imatinib via Bach2 in CML cells, we analyzed the localization and dynamics of Bach2. We found that Bach2 relocated from cytoplasm into cell nucleus and forms nuclear foci around PML body upon oxidative stress. Bach2 selectively repressed transcriptional activity associated with PML body. Furthermore, Bach2 required protein modification for the envelopment of PML body. Since PML is a known pro-apoptotic factor, these results suggest that Bach2 might induce apoptosis through the transcription repression of genes associated with PML body in CML cells after treatment with imatinib.
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Report
(3 results)
Research Products
(11 results)
