2014 Fiscal Year Final Research Report
Molecular mechanisms of disease progression in myeloproliferative neoplasms.
| Project/Area Number |
24591401
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | University of Miyazaki |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
SHIMODA Kazuya 宮崎大学, 医学部, 教授 (90311844)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | 骨髄増殖性腫瘍 / JAK2 / TET2 |
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| Outline of Final Research Achievements |
We examined the effects of JAK2 and TET2 mutations on myeloproliferative neoplasms (MPNs) development and disease progression. Recipients of JAK2V617F cells developed primary myelofibrosis-like features. The addition of TET2-loss worsened this phenotype. Double-mutant (JAK2V617F plus TET2-loss) myeloid cells were more likely to be in a proliferative state than JAK2V617F single-mutant cells. In a serial competitive transplantation assay, JAK2V617F cells resulted in decreased chimerism in the second recipients, which did not develop MPNs. In marked contrast, cooperation between JAK2V617F and TET2-loss developed and maintained MPNs in the second recipients. In-vitro sequential colony formation assays also supported the observation. We conclude that loss of TET2 has two different roles in MPNs: disease accelerator and disease initiator and sustainer in combination with JAK2V617F.
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| Free Research Field |
血液内科学
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