Analysis of residual disease using newly developed single cell RNA sequencing.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09926
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyoto University
• Principal Investigator: Nakagawa Masahiro 京都大学, 医学研究科, 特定講師 (10431850)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 単一細胞解析 / 白血病 / 骨髄異形成症候群

Outline of Final Research Achievements

We have developed a new single-cell analysis platform that can identify mutations with high sensitivity for the analysis of refractory clones in intratumor heterogeneity, which is a major factor in the therapy resistance of hematological malignancies. Using this method, hematopoietic progenitors derived from the bone marrow of healthy individuals or patients with hematological malignancies were analyzed. We found that apparently normal hematopoietic progenitors show aberrant expression profiles compared to normal cells in healthy controls without driver mutations. These results suggest that a favorable environment for the clone is important for their expansion and was considered to be an important finding for the realization of a new therapeutic intervention.

Free Research Field

造血器腫瘍

Academic Significance and Societal Importance of the Research Achievements

本研究で開発した、高感度にドライバー変異を同定可能な単一細胞RNAシーケンス技術の適用範囲は極めて広い。変異細胞を区別して解析可能なため、腫瘍の初期発生から、多様な変異を有する細胞が混在する腫瘍内多様性の解析などで、変異の及ぼす細胞自律性の影響だけで無く、腫瘍細胞と環境の相互作用などの非細胞自律性の解析も可能となる。腫瘍のクローン進化のさらなる理解と新規の治療法の開発に向けた大きな意義ある一歩であると考えられる。