Understanding of pathogenesis of Trisomy 8-induced myelodysplastic syndrome

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22640
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
• 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): 2019-06-28 – 2021-03-31
• Keywords: トリソミー8 / 骨髄異形成症候群 / 数的染色体異常 / 造血幹細胞 / クロマチン / キメラマウス

Outline of Final Research Achievements

It has long been known that chromosomal abnormalities are deeply involved in the development and progression of cancer. In myelodysplastic syndrome (MDS), numerical chromosomal abnormalities such as trisomy 8 and monosomy 7 are closely related to the pathophysiology and prognosis of MDS, and are also essential criteria for diagnosis and treatment selection. Although trisomy 8 has a relatively poor prognosis, the responsible gene and responsible region on chromosome 8 were not clarified due to the heterogeneity of MDS cells by examining only alteration of expression of genes in Chromosome 8. Under these circumstances, we introduced human chromosome 8 into mouse ES cells using artificial chromosome technology, created a +8 chimeric mouse, established a new MDS model, and analyzed the function of +8 hematopoietic stem cell.

Free Research Field

医学

Academic Significance and Societal Importance of the Research Achievements

数的染色体異常によるMDS発症機構の分子メカニズムは未だ明らかでない。本研究によって、こうしたMDSの病態基盤が解明されることで、病態に応じた治療法開発のための知見が期待できる。さらに、申請者の新規がん生体モデルによって、全く未知であった数的染色体異常によるがん発症機構の一端が理解できる。