2017 Fiscal Year Final Research Report
The role of HMGA2 in the pathogenesis of MPN
| Project/Area Number |
16K19582
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hematology
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
UEDA KOKI 福島県立医科大学, 医学部, 助教 (80632190)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | 骨髄増殖性腫瘍 / HMGA2 |
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| Outline of Final Research Achievements |
MPN are driven by mutations in JAK2, CALR and MPL.We have recently shown high HMGA2 mRNA level in almost all patients with myelofibrosis. Thus, to clarify if HMGA2 affect JAK2V617F+ hematopoiesis, we crossed HMGA2-overexpressing mice with JAK2V617F Tg mice. At 3 months old, leukocytosis, thrombocytosis, anemia and splenomegaly were most severe in double-Tg. Hmga2 and JAK2VF Tg mouse survived for over a year, but all double-Tg died within 5 months. Lineage-Sca1+Kit+ cells were most frequent in double-Tg followed by ∆Hmga2, indicating HMGA2 contributes to expansion of JAK2V617F+ hematopoietic stem cells (HSC). In competitive/serial transplants, ∆Hmga2 and double-Tg cells steadily expanded, while JAK2VF cells were decreased and eventually rejected in 3rd transplant. Thus, HMGA2 may accelerate proliferative hematopoiesis harboring JAK2V617F with expanding MPN HSC.
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| Free Research Field |
血液腫瘍
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