| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Research Abstract |
MLL gene is located in chromosome ll band q23 and is responsible for acute leukemias such as secondary leukemia, infantile leukemia, monocytic leukemia and so on. MLL is disrupted by 11q23 chromosomal translocations including t(4;11), t(9;11) and t(11;19), and is fused to partner genes resulting in the generation of chimeric proteins. MLL is thought to be a transcriptional regulator, although the target genes have not been identified. In this study, we have investigated MLL target genes responsible for leukemogenesis. Three transfectants were made, 32D-Zf(-) expressing truncated MLL gene MLL-Zf(-) which represents MLL chromosomal translocations, 32D-MLL expressing wild type MLL and 32D-VC which only include vector control. Gene(s) whose expression is different between transfectants were searched by means of RDA (representational difference analysis) analysis. PI-3 kinase gene was expressed in 32D-Zf(-) but not in 32D-VC. However, only this could not describe the leukemogenesis of mutant MLL gene, because the PI-3 kinase was also expressed in 32D-MLL. Further, we have performed RDA analysis with 32D-Zf(-) as a tester and 32D-MLL as a driver, and have identified that a-spectrin gene is specifically expressed in 32D-Zf(-) transfectant. These data suggest that co-expression of PI-3 kinase and a-spectrin genes plays an important role for the leukemogenesis of MLL gene translocations. Additional experiments are needed, which prove growth advantage and differentiation block when α-spectrin gene is introduced to 32D-MLL transfectant.
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