Stem cell-specific phosphorylation of Smad3 for regulating self-renewal capacity in CML stem cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 26290038
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Hiroshima University (2015-2016); Kanazawa University (2014)
• Principal Investigator: Naka Kazuhito 広島大学, 原爆放射線医科学研究所, 准教授 (70372688)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 慢性骨髄性白血病 / CML幹細胞 / チロシンキナーゼ阻害剤抵抗性 / 再発 / Smad3 / p38 MAPK / マウスモデル / 非臨床試験

Outline of Final Research Achievements

Although the discovery of tyrosine kinase inhibitors (TKIs) has been improved prognosis of chronic myelogenous leukemia (CML) patients, CML stem cells are responsible for the relapse of CML disease following TKI therapy. In this study, we found that the stem cell-specific phosphorylation of Smad3 at Ser208 residue plays an essential role for the maintenance of self-renewal capacity in CML stem cells in vivo. In addition, p38MAPK regulated the phosphorylation of Smad3 at Ser208. Indeed, we demonstrated that the administration of an inhibitor targeting p38MAPK significantly delayed the disease relapse of CML-affected mice.

Free Research Field

幹細胞生物学