2013 Fiscal Year Final Research Report
Identification of a critical epigenetic mechanism via histone modification in drug resistance of blood cancer cells.
| Project/Area Number |
23591405
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Jichi Medical University |
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Principal Investigator |
KIKUCHI Jiro 自治医科大学, 医学部, 准教授 (60371035)
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| Co-Investigator(Renkei-kenkyūsha) |
FURUKAWA Yusuke 自治医科大学, 医学部, 教授 (00199431)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 血液腫瘍学 / エピジェネティクス / 薬剤耐性 |
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| Research Abstract |
Cell adhesion mediated-drug resistance (CAM-DR) is a major obstacle in achieving cure in patients with hematologic malignancies including multiple myeloma (MM). We found that di or trimethylation was moderately induced in histone H3 lysine 4 (K4) and K36, and markedly in K9 and K27 by anti-MM drug treatment without adhesion to stromal cells. In contrast, trimethylation to K27 (H3K27me3) was absent in cell adhesion mediated-drug resistant MM cells. Inhibition of H3K27me3 significantly inhibited anti-MM drug-induced apoptosis in stroma free condition. These results suggest that cell adhesion-induced H3K27me3 inhibition is a critical step in drug resistance of MM cells.
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Research Products
(13 results)
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[Journal Article] Homopiperazine derivatives as a novel class of proteasome inhibitors with a unique mode of proteasome binding2013
Author(s)
Kikuchi J, Shibayama N, Yamada S, Wada T, Nobuyoshi M, Izumi T, Akutsu M, Kano Y, Sugiyama K, Ohki M, Park SY, and Furukawa Y
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Journal Title
PLoS One
Volume: 8
Pages: e60649
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[Journal Article] HOX-mediated LMO2 expression in embryonic mesoderm is recapitulated in acute leukaemias2013
Author(s)
Calero-Nieto FJ, Joshi A, Bonadies N, Kinston S, Chan WI, Gudgin E, Pridans C, Landry JR, Kikuchi J, Huntly BJ, and Gottgens B
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Journal Title
Oncogene
Volume: 32
Pages: 5471–5480
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[Journal Article] BCR-ABL regulates death receptor expression for TNF-related apoptosis-inducing ligand (TRAIL) in Philadelphia chromosome- positive leukemia2013
Author(s)
Kuroda I, Inukai T, Zhang X, Kikuchi J, Furukawa Y, Nemoto A, Akahane K, Hirose K, Honna-Oshiro H, Goi K, Kagami K, Yagita H, Tauchi T, Maeda Y, Sugita K
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Journal Title
Oncogene
Volume: 32
Pages: 1670-1681
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[Presentation] Homopiperazine derivatives as a novel class of proteasome inhibitors with a unique mode of proteasome binding2013
Author(s)
Kikuchi J, Shibayama N, Yamada S, Wada T, Nobuyoshi M, Izumi T, Akutsu M, Kano Y, Sugiyama K, Ohki M, Park SY, and Furukawa Y
Organizer
第75回日本血液学会学術集会
Place of Presentation
札幌
Year and Date
2013-10-12
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[Presentation] Homopiperazine derivatives as a novel class of proteasome inhibitors with a unique mode of proteasome binding2013
Author(s)
Kikuchi J, Shibayama N, Yamada S, Wada T, Nobuyoshi M, Izumi T, Akutsu M, Kano Y, Sugiyama K, Ohki M, Park SY, and Furukawa Y
Organizer
14^<th> International Myeloma Workshop
Place of Presentation
Kyoto, Japan
Year and Date
2013-04-03
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