| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Outline of Final Research Achievements |
We established patient-derived iPSCs of chronic myelomonocytic leukemia (CMML) by introducing episomal vectors with butyrate under hypoxic conditions. In a CMML patient, an unbalanced translocation der(1;7)(q10;p10) and mutations in EZH2, RUNX1, NRAS, and TP53 were detected in all CMML iPSCs clones. CMML iPSC-derived hematopoietic progenitor cells (HPCs) formed an increased number of hematopoietic colonies and recapitulated the profiles of the surface antigens of CMML in vitro. Phosphorylation of ERK was increased in CMML iPSC-derived HPCs, and a MEK or RAS inhibitor suppressed the colony-forming capacity. The human CMML mouse model was established by secondary transplantation of human CD45+ cells from teratomas generated from CMML iPSCs, which exhibited monocytosis and proliferation of blasts in the bone marrow. This novel CMML model generated using patient-derived iPSCs produced HPCs that recapitulated the properties of CMML.
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