Clonal architecture of myeloid malignancies as revealed by single-cell RNA sequencing.

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19595
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology and related fields
• Research Institution: Kyoto University
• Principal Investigator: OGAWA SEISHI 京都大学, 医学研究科, 教授 (60292900)
• Research Collaborator: Takaori Akiumi ; Miyano Satoru ; Nakagawa Masahiro
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: 骨髄異形成症候群 / 白血病 / クローン進展 / 単一細胞解析 / 腫瘍内多様性

Outline of Final Research Achievements

The development and progression of acute myeloid leukemia (AML) are shaped by multiple rounds of acquisition of new driver mutations and subsequent clonal selection. These clonal evolutions develop substantial intra-tumor heterogeneity, which is one of the major reasons of treatment failure and relapse.
Recent development of single-cell analysis method has provided a novel opportunity to understand this complexity, which however, is severely hampered by the difficulty to detect both mutations and expression profiles at the same time. To overcome this, we developed a robust method for simultaneous detection of both mutations and gene expression in this study.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

近年、一見正常に見える組織においても、加齢や生活習慣によりドライバー変異を有するクローンの拡大が見られることが、我々や他のグループによって明らかになっている。これらのクローン拡大は、がんの初期発生に重要と考えられるが、その詳細な機構は未だ明らかでない。本研究で開発した手法は、さらなる最適化により、様々な組織におけるこのようなクローン拡大の解析に利用可能であり、がんの初期発生の理解の進展に大きく寄与することが期待される。