Simultaneous single cell analysis of intracellular proteins and gene expressions in Acute myeloid leukemia

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16310
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Keio University
• Principal Investigator: Murakami Koichi 慶應義塾大学, 医学部(信濃町), 助教 (60846088)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 急性骨髄性白血病 / シングルセル解析 / 遺伝子発現解析 / 蛋白質発現解析

Outline of Final Research Achievements

In this study, we developed a novel method for simultaneous analysis of intracellular proteins including phosphorylated proteins at single-cell level in addition to gene expression and cell surface proteins using human peripheral blood and bone marrow samples. By applying this method to the samples from patients with newly diagnosed acute myeloid leukemia (AML) and comparing them with normal bone marrow samples from healthy donors, we identified intracellular proteins that are upregulated in myeloid cells and surrounding immune cells in the tumor compared to normal bone marrow cells. In the future, we will clarify the mechanism of intracellular protein expression changes and the resulting changes in cellular functions and tumor microenvironment using AML mouse models.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

本研究で開発した新規のシングルセル解析手法は、ヒト検体にも適用可能であり、今回解析対象とした急性骨髄性白血病以外の癌種や感染症、自己免疫疾患など多くの疾患研究に広く応用可能な手法である。また、本手法で見出された急性骨髄性白血病検体における単一細胞レベルでの細胞内蛋白質発現量の変化は、遺伝子発現および細胞表面蛋白質発現と同時に単一細胞レベルで解析したことで初めて明らかになったものであり、今後さらに研究を進めることで、この変化が及ぼす腫瘍進展への影響やその発生機序を明らかにすることで新たな治療標的候補を見出すことが期待出来る。