| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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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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