The elucidation of the mechanisms of growth arrest and apoptosis in myeloma cells induced by PU.1 and its utility for myeloma treatment
| Project/Area Number |
23591395
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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 | Kumamoto University |
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Principal Investigator |
OKUNO YUTAKA 熊本大学, 大学院生命科学研究部, 准教授 (80363539)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 多発性骨髄腫 / PU.1 / 細胞増殖停止 / 細胞死 / 癌抑制遺伝子 / B細胞リンパ腫 / M蛋白 / 腫瘍抑制因子 / ホジキンリンパ腫 / p21 / TRAIL |
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| Research Abstract |
We conditionally expressed PU.1 in classical Hodgkin lymphoma cell lines, L-428 and KM-H2, and identified that PU.1 induced growth arrest and apoptosis in these cells. Lentiviral transduced PU.1 expression also induced apoptosis in primary Hodgkin lymphoma cells from patients. Therefore, we concluded that PU.1 is a potent tumor suppressor in classical Hodgkin lymphoma cells.
We previously conditional expressed PU.1 also induces growth arrest and apoptosis in myeloma cell lines, U266 and KMS12PE. To test whether PU.1 is a tumor suppressor in mature B cells, including plasma cells, in vivo, we generated conditional PU.1 knockout mice in post germinal center B cells and plasma cells. At the age of 18-24 months, some of these mice shows a proliferation plasma cells in spleen and/or bone marrow. Therefore, PU.1 might be a tumor suppressor in plasma cells in vivo. We are still analyzing these mice.
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Report
(4 results)
Research Products
(29 results)
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[Journal Article] PU.1 is a potent tumor suppressor in classical Hodgkin lymphoma cells2013
Author(s)
Yuki H, Ueno S, Tatetsu H, Niiro H, Iino T, Endo S, Kawano Y, Komohara Y, Takeya M, Hata H, Okada S, Watanabe T, Akashi K, Mitsuya H and Okuno Y
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Journal Title
Blood
Volume: 121(6)
Pages: 962-970
Related Report
Peer Reviewed
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[Journal Article] PDK1 inhibition is a novel therapeutic target in multiple myeloma.2013
Author(s)
Fujiwara, S., Kawano, Y., Yuki, H., Okuno, Y., Nosaka, K., Mitsuya, H., and Hata, H.
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Journal Title
Br J Cancer
Volume: 108
Issue: 1
Pages: 170-178
DOI
Related Report
Peer Reviewed
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[Journal Article] Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide.2012
Author(s)
Kawano, Y., Fujiwara, S., Wada, N., Izaki, M., Yuki, H., Okuno, Y., Iyama, K., Yamasaki, H., Sakai, A., Mitsuya, H., et al.
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Journal Title
Int J Oncol
Volume: 41
Issue: 3
Pages: 876-884
DOI
Related Report
Peer Reviewed
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[Journal Article] RUNX1 regulates the CD34 gene in haematopoietic stem cells by mediating interactions with a distal regulatory element2011
Author(s)
Levantini E, Lee S, Radomska H, Hetherington C, Alberich-Jorda M, Amabile G, Zhang P, Gonzalez D, Zhang J, Basseres D, Wilson N, Koschmieder S, Huang G, Zhang D, Ebralidze A, Bonifer C, Okuno Y, Gottgens B, Tenen DG
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Journal Title
EMBO J
Volume: 30(19)
Pages: 4059-4070
Related Report
Peer Reviewed
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[Presentation] Conditional knockout of PU.1 in plasma cells results in monoclonal gammopathy2013
Author(s)
Shinya Endo, Hiromichi Yuki, Yoshihiro Komohara, Shikiko Ueno, Hiro Tatetsu, Motohiro Takeya, Seiji Okada, Koichi Akashi, Daniel G Tenen, Hiroaki Mitsuya, Yutaka Okuno
Organizer
日本血液学会
Place of Presentation
ロイトン札幌
Year and Date
2013-10-11
Related Report
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