Functional analysis of CD35-positive leukemic stem cells and identification of candidate molecules for targeted therapy

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08755
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kyushu University
• Principal Investigator: Mori Yasuo 九州大学, 大学病院, 助教 (90573345)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: CD35 / 白血病幹細胞 / 補体経路 / 治療標的

Outline of Final Research Achievements

In our study, the presence of CD35-positive subfraction was identified in 28.8±11.3% of the leukemic stem cell (LSC) population. This CD35+ LSCs were significantly enriched in the CD34+CD38-CD45RA-Tim3+ fraction. We performed functional assays by using FACS-purified CD35+/- LSC fraction. Although a trend towards less complement binding in the CD35+ LSCs was observed, no differences in survival or colony-forming capacity were evident between these CD35+/- LSCs in vitro cell culture with or without the complement supplementation. Further comparative analysis of gene and protein expression is required to clarify the functional characteristics of the CD35+ LSCs and the specific molecules and signaling pathways that could be therapeutic targets. In addition, we are planning to assess the impact of residual CD35+ LSCs on clinical outcomes by using samples that are acquired from the patients experienced leukemia relapse.

Free Research Field

血液学　造血細胞移植　幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

我々が造血幹細胞マーカーとして見出したCD35の発現は、白血病幹細胞(LSC)分画にも見出された。既知のLSCマーカーであるTim-3との共発現パターンから機能的なLSCの分離・純化に有用であると考えられ、今後のLSC研究に利用可能な有意義が結果が得られたものと考えている。一方で、研究期間内には治療法開発に直結するデータの創出には至らず、CD35+Tim-3+LSCでより特異的に発現する分子や特徴的なシグナル経路の抽出など、実臨床への応用に向けた研究継続の必要性を認識している。