Development of an evaluation method based on the elucidation of drug-resistance mechanisms of leukaemia cells through bone marrow niche cross talk

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07425
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Tokai University
• Principal Investigator: MIYACHI Hayato 東海大学, 医学部, 教授 (20174196)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 白血病 / 抗がん剤抵抗性 / 細胞外マトリックス / 骨髄ニッチ

Outline of Final Research Achievements

In the treatment of acute leukemia patients, drug-resistance after therapy with chemotherapeutic agents is clinically problematic. The residual disease after the therapy survives and re-proliferates through bone marrow niche cross-talk. This study was undertaken to elucidate drug-resistance mechanisms of leukemia cells through bone marrow niche cross talk, and to development of an evaluation method based on it. Cultured leukemia cell lines with FLT3-ITD showed collateral resistance to are-C in the presence of fibronectin or G-CSF, which can derive from stromal cells in bone marrow. This crosstalk can be target of evaluation and interruption for the overcome.

Free Research Field

臨床検査学

Academic Significance and Societal Importance of the Research Achievements

急性白血病の治療において、抗がん剤に対する治療抵抗性（耐性）は患者診療上の重要な課題で、耐性の分子機構の解明とそれに基づく、診断と克服法への応用は治療成績の向上につながると期待される。治療後に残存した白血病細胞は、骨髄（腔内）微小環境（ニッチ）内に潜伏し、その再増殖が再発、治療抵抗性の原因となる。本研究では、治療後骨髄ニッチ内に残存し、予後不良の原因となる白血病細胞の耐性の分子機構を明らかにした。これらに重要な分子は、治療抵抗性の診断と治療法の開発を通して、個別患者に最も適切な治療法の選択と治療予後の改善に貢献しうると考えられる。