The mouse model using patient-derived iPSCs recapitulates chronic myelomonocytic leukemia
| Project/Area Number |
25893048
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TAOKA Kazuki 東京大学, 医学部附属病院, 助教 (30529178)
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| Project Period (FY) |
2013-08-30 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| 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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| Keywords | iPS / 白血病 / 血液内科 |
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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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Report
(3 results)
Research Products
(2 results)
