Budget Amount *help |
¥186,550,000 (Direct Cost: ¥143,500,000、Indirect Cost: ¥43,050,000)
Fiscal Year 2018: ¥36,010,000 (Direct Cost: ¥27,700,000、Indirect Cost: ¥8,310,000)
Fiscal Year 2017: ¥36,010,000 (Direct Cost: ¥27,700,000、Indirect Cost: ¥8,310,000)
Fiscal Year 2016: ¥36,140,000 (Direct Cost: ¥27,800,000、Indirect Cost: ¥8,340,000)
Fiscal Year 2015: ¥36,010,000 (Direct Cost: ¥27,700,000、Indirect Cost: ¥8,310,000)
Fiscal Year 2014: ¥42,380,000 (Direct Cost: ¥32,600,000、Indirect Cost: ¥9,780,000)
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Outline of Final Research Achievements |
It has been clarified that age-related clonal hematopoiesis (ARCH) is closely involved in the development process of MDS and AA. Furthermore, we elucidated the molecular pathogenesis of RNA spliceosome mutations that are frequently observed in MDS and ARCH. ARCH was not found in Werner syndrome (WS) patients as well as in MDS that developed from WS, suggesting the existence of different aging and tumor development mechanisms. We found that gene mutations identical to CLL cells were acquired at the hematopoietic stem cell level in most of CLL cases, and identified IRAK-3 molecules ectopically expressed in CLL cells as a tumorigenic mechanism from CLL stem cells. It was shown that tumor cells secrete galectin-9, which is a ligand of TML-3, a stem cell-specific molecule of AML, into autocrine. Using the CRISPR / Cas9 system, mice with deletion alleles of Wrn and senescence related gene and double deletion mice were generated.
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