The role of HMGA2 in the pathogenesis of HMGA2

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860720
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Fukushima Medical University
• Principal Investigator: UEDA KOKI 福島県立医科大学, 医学部, 助教 (80632190)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 骨髄増殖性腫瘍 / HMGA2

Outline of Final Research Achievements

To clarify if HMGA2 affect JAK2V617F+ hematopoiesis, we crossed HMGA2-overexpressing mice (ΔHmga2) with JAK2V617F Tg mice (JAK2VF) and obtained ΔHmga2-JAK2VF mice (double-Tg). At 3 months old, leukocytosis, thrombocytosis, anemia and splenomegaly were most severe in double-Tg compared with ΔHmga2 or JAK2VF. ΔHmga2 and JAK2VF 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 ΔHmga2, indicating HMGA2 contributes to expansion of JAK2V617F+ hematopoietic stem cells (HSC). In competitive/serial transplants, ΔHmga2 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. In fact, endogenous HMGA2 is upregulated in JAK2VF with conditional EZH2 KO (EZH2-/-JAK2VF).

Free Research Field

骨髄増殖性腫瘍