2010 Fiscal Year Final Research Report
Toward the comprehensive understanding of molecular mechanisms of hematopoietic malignancies
| Project/Area Number |
20249051
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KITAMURA Toshio The University of Tokyo, 医科学研究所, 教授 (20282527)
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| Co-Investigator(Kenkyū-buntansha) |
KITAURA Jiro 東京大学, 医科学研究所, 助教 (30282651)
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| Co-Investigator(Renkei-kenkyūsha) |
YUJI Koichiro 東京大学, 医科学研究所, 助教 (50396868)
TOJO Arinobu 東京大学, 医科学研究所, 教授 (00211681)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 発現クローニング / レトロウィルスベクター / AML1 / MDS / 遺伝子変異 |
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| Research Abstract |
We studied the molecular mechanisms of etiology of leukemia, myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) mainly through the usage of mouse bone marrow transplant (BMT) model. Mutations involved in leukemogenesis are classified into two major groups : class I mutations induced proliferation or block apoptosis while class II mutations hamper differentiation of hemopoietic cells. In this research project, we have shown using a mouse BMT model that class I mutations induce MPN, that class II mutations induce MDS and that combination of class I and class II mutations induce acute leukemia. We have also indicated that additional class I mutations such as FLT3-ITD or overexpression of Evi1 could lead to progression of MDS to overt leukemia and that additional class mutations such as overexpression of Hes1 could result in progression of MPN to acute leukemia, blast crisis of CML. Thus, the combinations of mutations and the timing of each mutation will determine the disease course of MDS/overt leukemia, MPN/overt leukemia and acute leukemia.
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[Journal Article] Two types of C/EBPa mutations play distinct roles in leukemogenesis: Lessons from clinical data and BMT models2011
Author(s)
Kato N., Kitaura J., Doki N., Komeno Y., Watanabe-Okochi N., Togami K., Nakahara F., Oki T., Enomoto Y., Fukuchi Y., Nakajima H., Harada Y., Harada H., Kitamura T.
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Journal Title
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[Journal Article] Hesl immortalizes committed progenitors and plays a role in blast crisis transition in chronic myelogeneou leukemia2010
Author(s)
Nakahara F., Sakata-Yanagimoto M., Komeno Y., Kato N., Uchida T., Haraguchi K., Kumano K., Harada Y., Harada H., Kitaura J., Ogawa S., Kurokawa M., Kitamura T., Chiba S.
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Journal Title
Blood 115
Pages: 2872-2881
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[Journal Article] AID-induced T-lymphoma or B-leukemia/lymphoma in a mouse BMT model2010
Author(s)
Komeno Y., Kitaura J., Watanabe-Okochi N., Kato N., Oki T., Nakahara F., Harada Y., Harada H., Shinkura R., Nagaoka H., Hayashi Y., Honjo T., Kitamura T.
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Journal Title
Leukemia 24
Pages: 1018-1024
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[Journal Article] Possible involvement of RasGRP4 in leukemogenesis2009
Author(s)
Watanabe-Okochi N., Oki T., Komeno Y., Kato N., Yuji K., Ono R., Harada Y., Harada H., Hayashi Y., Nakajima H., Nosaka T., Kitaura J., Kitamura T.
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Journal Title
Int J.Hematology 89
Pages: 470-481
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[Presentation] Molecular Basis for AML2010
Author(s)
Kitamura T., Nakahara F., Kato N., Watanabe-Okochi N., Komeno Y., Doki N., Togami K., Uchida T., Kagiyama Y., Inoue D., Enomoto Y., Oki T., Harada H., Kitaura J.
Organizer
MDS and MPN 第39回国際実験血液学会
Place of Presentation
メルボルン(招待講演)
Year and Date
20100915-20100918
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