Development of novel therapies targeting the interaction between tumor cells and their unique microenvironments for hematological malignancies

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02950
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kyushu University
• Principal Investigator: Kunisaki Yuya 九州大学, 医学研究院, 教授 (80737099)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 造血幹細胞 / 造血微小環境 / 加齢

Outline of Final Research Achievements

Functions of hematopoietic stem cells (HSCs) required for the hematopoietic homeostasis are tightly regulated by their unique microenvironments (niches) in bone marrow. Previous studies have revealed that bone marrow mesenchymal stem cells are an essential player to keep HSCs quiescent that is a key behavior of stem cells to protect them from being exhausted and malignant transformation by exogenous insults. This study reveals the contribution of bone marrow microenvironments altered with aging to the pathogenesis, clonal evolution and leukemic transformation in myelodysplastic syndrome (MDS).
Leukemia stem cells are regulated by circadian clock genes whose regulator is a therapeutic target for leukemia. Previously, by performing a screen for small compounds that inhibited the circadian clock, we found a CK2 inhibitor, GO289 exhibiting inhibitory effects on leukemia cell lines in vitro.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

新規シングルセルシーケンスであるDrop-seqと３次元イメージングという2つの新技術を組み合わせた解析により細胞間の相互作用の理解し、間葉系幹細胞をその機能により分類することができた本研究成果は、骨修復や骨病変を来す病態のより深い理解、ひいては効率的な骨再生や新たな骨病変治療薬の開発にも繋がると期待される。更に、加齢に伴う「ニッチ」と幹細胞相互作用の変化を解明し、その知見をヒト造血器腫瘍に応用することで、微小環境を標的とした新たな造血器腫瘍治療法の開発へも繋がると期待される。