| Project/Area Number |
22790904
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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 | Tokai University (2011)
The University of Tokyo (2010) |
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Principal Investigator |
KOTANI Ai 東海大学, 創造科学技術研究機構, 特任准教授 (00517477)
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | miRNA / 細胞運命決定 / 急性リンパ性白血病 / 細胞運命 / IRS1 |
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| Research Abstract |
MicroRNAs(miRNAs) are small noncoding RNAs vital to many cell functions that act post-transcriptionally to decrease the expression of target mRNAs. In this study we investigated miRNA involvement in cell differentiation in acute leukemia. In ALLs with MLL rearrangement, the expression of miR-126 is downregulated compared to other types of ALLs. When we restored miR-126 expression in a cell line derived from an MLL-AF4 ALL patient(SEM), B cells markers CD20 and CD19 were significantly upregulated, suggesting that miR-126 had induced B cell differentiation in MLL-AF4 ALL. A cDNA array measuring gene expression also showed upregulation of B cell related genes in SEM cells overexpressing miR126.When we overexpressed miR-126 in normal hematopoietic cells in vivo via mouse bone marrow transplantation, we also observed an increase in the number of CD19+cells in the peripheral blood, revealing that miR-126 induces B cell differentiation both in leukemia and normal hematopoietic cells. The mechanism of B cell differentiation by miR-126 was investigated using the coculture system of mouse fetal liver cells and TSt-4 stromal cells, which showed that miR-126 induces differentiation in uncommitted cells but not in cells committed to a lymphoid or myeloid lineage.
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