2011 Fiscal Year Final Research Report
Establishment of murine model of Evi1-related leukemia and development of radical cure.
| Project/Area Number |
22790899
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
OKOCHI Naoko 東京大学, 医学部附属病院, 助教 (00568412)
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| Project Period (FY) |
2010 – 2011
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| Keywords | 血液腫瘍学 |
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| Research Abstract |
Ecotropic viral integration site 1(Evi1) is one of the master regulators in the development of acute myeloid leukemia(AML) and myelodysplastic syndrome(MDS). High expression of Evi1 is found in 10% of AML patients and indicates a poor outcome. Several recent studies indicate that Evi1 requires collaborative factors to induce AML. Therefore, the search for candidate factors which collaborate with Evi1 in leukemogenesis is one of the key issues in uncovering the mechanism o Evi1-related leukemia. Previously, we succeeded in making a mouse model of Evi1-related leukemia using a bone marrow transplantation(BMT) system. In the Evi1-induced leukemic cells, we identified frequent retroviral integrations near the CCAAT/Enhancer-binding Proteinβ(C/EBPβ) gene and overexpression of its protein. These findings imply that C/EBPβis a candidate gene which collaborates withEvi1 in leukemogenesis. Co-transduction of Evi1 and the shortest isoform of C/EBPβ, Liver Inhibitory Protein(LIP), induced AML with short latencies in a mouseBMT model. Overexpression of LIP alone also induced AML with longer latencies. However, excision of all three isoforms of C/EBPβ(LAP*/LAP/LIP) did not inhibitthe development of Evi1-induced leukemia. Therefore, isoform-specific intervention that targets LIP is required when we consider C/EBPβas a therapeutic target.
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