Exploring the mechanism of mutation acquisition to induce tumorigenesis using Down syndrome associated leukemia model

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17358
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kyoto University
• Principal Investigator: Nishinaka-Arai Yoko 京都大学, 医学研究科, 助教 (80789644)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 一過性骨髄異常増殖症 / 発がん

Outline of Final Research Achievements

Gene mutation acquisition mechanism which induced tumorigenesis was analyzed using the disease model applicable to the multi-step tumorigenesis theory.
We performed experiments that pluripotent stem cell pairs of disomy 21 (d21) and trisomy 21 (t21) clones were used and compared at each hematopoietic differentiation stage.
As a result, in the process of mutation acquisition and DNA damage repair, no significant difference was observed between d21 and t21 clones until early hematopoietic progenitor cells. On the other hand, the cell proliferation activity was not significantly different at the undifferentiated stage, but in hematopoietic progenitor cell stage, there was a tendency for increased cell cycle in t21 clones.

Free Research Field

小児血液学

Academic Significance and Societal Importance of the Research Achievements

がんは日本人の死因第1位として知られており、その発生・進展は、ゲノム変異の蓄積によるクローン進化を基本原理とする、いわゆる多段階発がん説によって説明される。本研究は、多段階発がんのモデルとして知られるダウン症に合併する白血病に着目し、疾患特異的iPS細胞を用いて、その発症メカニズムを解析したものである。特色としては、細胞が遺伝子変異を獲得する流れを3段階に分けて定義することで、解析を可能としたことにあり、この定義は今回の対象疾患に留まらず、他のがん解析にも応用出来るものであると考えられる。