2003 Fiscal Year Final Research Report Summary
Molecular analysis of Ikaros gene family in hematologic malignancy
| Project/Area Number |
14570981
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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 |
Hematology
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
ISHIMARU Fumihiko Okayama University, Hospital, Assistant Professor, 医学部・歯学部附属病院, 講師 (50284097)
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| Co-Investigator(Kenkyū-buntansha) |
TANIMOTO Mitsune Okayama University, Graduate School of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (10240805)
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| Project Period (FY) |
2002 – 2003
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| Keywords | hematologic malignancy / transcription factor / Ikaros |
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| Research Abstract |
We analyzed expression of the transcription factor Ikaros in patients with hematologic malignancies and found that patients with blast crisis of chronic myelogenous leukemia (CML) overexpressed the dominant-negative isoform of Ikaros, Ik-6. Since patients with chronic phase of CML never overexpressed Ik-6, it is suggested that Ikaros might be involved in the disease progression of CML. We also demonstrated that patients with acute lymphoblastic leukemia (B cell) overexpressed Ik-6. These results suggest that Ikaros may play an important role as a tumor suppressor gene.
Using the bone marrow transplantation model, we introduced retrovirus vector alone (pMX/GFP or MSCV/NGFR) or Ik-6 (pMX/Ik-6/GFP or MSCV/Ik-6/NGFR) into mice and compared the survival. Although mice with vector alone were alive, mice with Ik-6 suffered leukemia 3-4 months after bone marrow transplantation and died. Mice with leukemia showed hepatosplenpmegaly, lymph node swelling, and thymoma. In the peripheral blood and bone marrow, leukemic cells with T cell phenotype (CD4+ CD8+) were observed.
Our study clearly shows that overexpression of Ik-6, found in patients with hematologic malignancies, is sufficient to cause leukemia in vivo. Ik-6 would be an excellent target of treatment and a good marker of minimal residual disease.
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Research Products
(5 results)
