| Project/Area Number |
18591082
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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 | Wakayama Medical University |
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Principal Investigator |
SONOKI Takashi Wakayama Medical University, School of Medicine, Associate Professor (30382336)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Lymphoid malignancies / Oncogenesis / microRNA125b-1 / microRNA142 / microRNA |
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| Research Abstract |
We found two patients of acute B-lymphoblastic leukemia (B-ALL) showing juxtaposition of immunoglobulin heavy chain (IGH) gene and microRNA125b1 (miR125b1). The two patients were young (24 and 26 years old) and the immunnophenotypes of both leukemic cells showed highly similar pattern. These observations suggested that dysregulated expression of miR125b1 resulting from juxtaposition of IGH gene might define a unique subset of B-ALL. Although we have analyzed fifteen patients including pediatric cases on genomic alterations of miR125b1, we found no additional cases exhibiting the miR125b1 abnormality. To investigate biological roles of dysregulated miR125b1 expression, we constructed expression recombinants that have miR125b1 under CMV promoter. After transfection of the expression recombinants to NIH3T3 cell or Ba/F3 cell, the transfected-cells showed altered life-span. Analyses of molecular bases of the altered life-span are now undergoing. We also found a case of aggressive lymphoma showing over expression of three genes, Cyclin D3, C-MYC, and microRNA142 (miR142). Transfection experiments using expression vector containing miR142 showed no obvious phenotypic changes; suggesting sole -overexpression of miR142 do not affect cell growth or death. We have now established co-transfection system of C-MYC, Cyclin D3 and miR142 genes mimicking multistep onocogenesis.
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