Specific DNA damage repair mechanisms in leukemic stem cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09935
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Yokohama City University
• Principal Investigator: Miyazaki Takuya 横浜市立大学, 附属病院, 助教 (20711245)
• Co-Investigator(Kenkyū-buntansha): 中島 秀明 横浜市立大学, 医学研究科, 教授 (30217723)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 白血病幹細胞 / DNA修復 / 急性骨髄性白血病

Outline of Final Research Achievements

Leukemic stem cell is thought to be a critical factor for chemotherapy resistance or relapse in acute myeloid leukemia (AML). Using flow cytometry, we tried to identify leukemic stem cell population, CD34+/CD38- cells in bone marrow or peripheral blood samples from patients with newly diagnosed or relapsed AML. Leukemic stem cells were sorted based on the CD34+/CD38- expression, which were minor population (1.91% (0.83-3.24%)), and RNA and proteins were extracted for DNA repair analysis. AML-related mutations were also identified by targeted sequencing. The target molecule, which is critical for DNA repair in leukemic stem cells, will be determined in the future study.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

本研究は、白血病幹細胞に特徴的なDNA修復メカニズムに着目して急性骨髄性白血病の再発や治療抵抗性に及ぼす影響を検証したものである。研究期間内に、白血病幹細胞特異的にDNA修復に影響する標的分子を同定することができず、その特徴的な細胞特性に関する知見は得られなかった。今後の展望として、白血病幹細胞の病態をより確実に捉えるべく実臨床における検体を用いた解析を継続し、急性骨髄性白血病の再発や治療抵抗性のメカニズムを解明していく。