Infection stresses promote the pathogenesis of myelodysplastic syndrome

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02842
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kumamoto University
• Principal Investigator: Sashida Goro 熊本大学, 国際先端医学研究機構, 特別招聘教授 (70349447)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 骨髄異形成症候群 / 感染症 / クローン造血 / ゲノム変異 / エピゲノム / クロマチン

Outline of Final Research Achievements

Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disease of aged adults characterized by impaired hematopoiesis and predisposition to acute myeloid leukemia. By utilizing our infection stress-induced Tet2-deficient MDS model, we will understand the mechanism of how hematopoietic stem cells promote the initiation and propagation of MDS due to stem cells heterogeneity in epigenetic changes and impaired homeostasis in hematopoietic and non-hematopoietic tissues upon the insults of infection stresses. Lastly, we will clarify the molecular mechanism of pathogenesis of MDS and give a rationale for novel therapeutic strategy for the prevention of and eradication of MDS cells.

Free Research Field

医学

Academic Significance and Societal Importance of the Research Achievements

加齢が慢性疾患やがんの発症をもたらすと信じられているが、複雑な生体内の生物学的応答のうちで、何が老化に伴ってがんになる原因であるかは不明である。本研究成果が進展することで、加齢幹細胞また前がん幹細胞が、感染罹患で生じたエピゲノム変化を蓄積・継承してMDS発症に至る分子基盤を理解できる。