Strategy aiming at the inhibition of leukemic evolution of the myelodysplastic syndromes by the use of MDS-derived cell lines

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03582
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Kawasaki Medical School
• Principal Investigator: Tohyama Kaoru 川崎医科大学, 医学部, 教授 (80227561)
• Co-Investigator(Kenkyū-buntansha): 通山 由美 姫路獨協大学, 薬学部, 教授 (70362770) ; 片岡 浩巳 川崎医療福祉大学, 医療技術学部, 教授 (80398049)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 骨髄異形成症候群 / 白血病化 / 遺伝子変異 / シングルセル解析

Outline of Final Research Achievements

To explore the molecular mechanism of disease progression from myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML), we performed single-cell RNA sequencing analysis using a series of six cell lines established from a patient with MDS. We attempted to explore the molecular mechanisms by which clones with different gene expression profiles develop the malignant process.
In the process of transformation from MDS-like to AML-like, we found a clear increase in CD34-positive cell fraction, loss of functional molecules specific to granulocytes such as S100A8, as well as changes in specific gene clusters. We expect to be able to identify a small number of candidate genes that may play key roles in this process, and further analysis is underway.

Free Research Field

造血器腫瘍を中心とする検査血液学

Academic Significance and Societal Importance of the Research Achievements

MDSは血球減少に加えてAMLに移行しやすい難治性造血障害で、とくにMDS由来のAMLはきわめて予後不良のため、画期的治療法が待望されている。本研究では申請者が樹立したMDSからAMLへの移行を表現した細胞株を用いて、悪性転換の鍵となる遺伝子変化を突き止めることに繋がることが期待される。解析すべきデータが膨大なため、さらに検討を進める必要があるが、新規治療の開拓に向けてあらたな分子標的を発見できる可能性がある。