Elucidation of molecular mechanism of multistep leukemogenesis by scRNA sequence

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15121
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Kyoto University
• Principal Investigator: Sakamoto Satoko 京都大学, 医学研究科, 研究員 (70648427)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 遺伝子発現解析 / メチル化解析 / シングルセル解析 / ダウン症候群 / 白血病

Outline of Final Research Achievements

To address molecular basis of Down syndrome’s acute megakaryo blastic leukemia (AMKL), we employed DNA methylation analysis and found DNA methylation profile of the AMKL was similar to the that of common myeloid progenitors (CMPs) and megakaryocyte/erythroid-progenitors (MEPs). We then conducted single cell RNA-sequencing of iPS cell-derived hematopoitic cells and could describe trajectory of differentiation. However, quality of scRNA-seq of leukemia cells was not sufficient for further analyses.

Free Research Field

ゲノム科学

Academic Significance and Societal Importance of the Research Achievements

遺伝子変異の蓄積が白血病をはじめとするがんの多段階発症に関与することが知られている。本研究では、遺伝子発現解析およびメチル化解析の両方から、正常の血球前駆細胞（HSC, MPP, CLP, CMP, GMP, MEP）、TAM、DS-AMKL由来細胞の特徴や違いを捉え、TAM, AMKL細胞の起源細胞の推定を行った。本研究により、TAM、AMKLにおける多段階白血病発症機構のさらなる理解が進むものと考えられる。