Analysis of transcriptional dysregulation mechanisms in Down syndrome-related Leukemia

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08249
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Hirosaki University
• Principal Investigator: Kanezaki Rika 弘前大学, 医学研究科, 助教 (60722882)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 転写因子 / 白血病

Outline of Final Research Achievements

Approximately 10% of newborns with Down syndrome develop a transient abnormal myelopoiesis (TAM), a disease characterized by the transient proliferation of immature megakaryocytes. Most TAMs go into remission, but a high percentage of patients develop megakaryocytic leukemia (ML-DS). The purpose of this study is to elucidate the molecular mechanisms of ML-DS development in order to prevent ML-DS transition and improve prognosis.
In our recent study, mutations in factors that function (or are thought to function) in cooperation with GATA1, a transcription factor essential for megakaryocyte differentiation, were frequently detected in ML-DS (unpublished). Based on the hypothesis that disregulation of gene expression centered on GATA1 is a common mechanism in the development of ML-DS, the regulatory mechanisms of gene expression involved in the pathogenesis of leukemia were investigated.

Free Research Field

小児血液学

Academic Significance and Societal Importance of the Research Achievements

TAMからML-DSへ進展する分子メカニズムを解明することは、ML-DS発症を予防する上で重要であり、ML-DSの新たな治療法を開発する際にも必要な知見となる。また、本研究における転写因子の機能解析データを提供することは、医学のみならず基礎的な分子生物学分野の発展に対しても貢献しうるものと考える。