Elucidation of molecular machineries for the regulation of myeloid leukemia stem cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 16H06391
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: Kyushu University
• Principal Investigator: AKASHI KOICHI 九州大学, 医学研究院, 教授 (80380385)
• Co-Investigator(Kenkyū-buntansha): 竹中 克斗 愛媛大学, 医学系研究科, 教授 (30301295) ; 菊繁 吉謙 九州大学, 医学研究院, 講師 (40619706) ; 曽我 朋義 慶應義塾大学, 環境情報学部(藤沢), 教授 (60338217) ; 宮本 敏浩 九州大学, 医学研究院, 准教授 (70343324) ; 国崎 祐哉 九州大学, 大学病院, 准教授 (80737099)
• Project Period (FY): 2016-05-31 – 2021-03-31
• Keywords: 白血病幹細胞 / TIM-3 / 治療抵抗性残存白血病 / メタボロミクス

Outline of Final Research Achievements

We previously reported that TIM-3 is universally expressed malignant hematopoietic stem cells of human myeloid malignancies such as acute myelogenous leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPN). TIM-3 is a functional molecule involved in the pathogenesis of human myeloid malignancies via utilizing TIM-3/galectin-9 autocrine loop. In this study, we focused on molecular mechanisms underlying the maintenance of stemness in human LSCs through the investigation of TIM-3-signaling and other LSCs-specific molecules that human myeloid LSCs universally depend upon. Through performing the multi-omics analysis, we successfully identified several novel LSCs-specific molecular or metabolic mechanisms including the downstream molecules involved in TIM-3-signaling. Furthermore, we also established the therapeutic models of human AML via targeting the novel LSCs-specific molecules in the project.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

本研究から得られた知見は、ヒト骨髄性腫瘍において、TIM-3シグナルを含めて白血病幹細胞を標的とした治療戦略の合理性を担保するものである。さらに複数のプロジェクトを有機的に結合させることで、新規のヒト白血病幹細胞特異的な治療標的分子群を同定することに成功し、今後の新規研究への発展性も高い研究を遂行することができたと考えられる。