2016 Fiscal Year Final Research Report
The pathogenesis of myeloproliferative neoplasms induced by TET2 mutation
| Project/Area Number |
26461408
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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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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 骨髄増殖性腫瘍 / TET2 / JAK2 |
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| Outline of Final Research Achievements |
Acquired mutations of JAK2 and TET2 are frequent in myeloproliferative neoplasms (MPNs). We examined the individual and cooperative effects of these mutations on MPN development. Recipients of JAK2V617F cells developed MPNs, and the addition of loss-of-TET2 worsened this JAK2V617F-induced disease. In a serial competitive transplantation assay, JAK2V617F cells resulted in decreased chimerism in the 2nd recipients, which did not develop MPNs. In contrast, cooperation between JAK2V617F and loss-of-TET2 developed and maintained MPNs in the 2nd recipients by compensating for impaired hematopoietic stem cell (HSC) functioning. Transcriptional profiling revealed that loss-of-TET2 affected the expression of many HSC signature genes. We conclude that loss-of-TET2 has two different roles in MPNs; one is as a disease accelerator, while the other is as a disease initiator and sustainer in combination with JAK2V617F.
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| Free Research Field |
血液内科学
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