Molecular mechanisms of ineffective hematopoiesis in myelodysplastic syndromes

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461409
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Fukushima Medical University
• Principal Investigator: Shikama Yayoi 福島県立医科大学, 医学部, 教授 (40291562)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 骨髄異形成症候群 / 好中球 / c-Fos / miR-34a / miR-155 / TNF-alpha / migration

Outline of Final Research Achievements

We found that c-Fos was reduced via overexpression of miR-34a and miR-155 in neutrophils isolated from patients with myelodysplastic syndromes (MDS). The reduction of c-Fos, which inhibited binding of NF-kB p60 to the promotor region of TNF-alpha DNA, induced overexpression of TNF-alpha under inflammation or oxidative stress (Shikama et al, PLoS One, 2016). The overexpression of miR-34a and miR-155 interfered with expression of Cdc42-specific guanine nucleotide exchange factors DOCK8 and FGD4, and a Rho family member Rac1, resulting in impairment in migration of MDS neutrophils toward fMLP and IL-8 (Cao et al, J Immunol, 2017).

Free Research Field

血液内科学　骨髄異形成症候群