Elucidation of proteasome inhibitor sensitivity determination mechanism in AL amyloidosis

• Project/Area Number: 18K07322
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Shinshu University
• Principal Investigator: Katoh Nagaaki 信州大学, 学術研究院医学系(医学部附属病院), 准教授 (30570014)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2022: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
• Keywords: ALアミロイドーシス / プロテアソーム阻害剤 / 免疫調整薬（IMIDs） / 治療感受性 / 形質細胞染色体異常

Outline of Final Research Achievements

Cases and samples were collected, and measurements and experiments were performed using the samples. Some results of the obtained clinical study (case study) part were reported in Shinshu Med J. 2022 70(1):29-38. It was suggested that treatment of patients with AL amyloidosis with a proteasome inhibitor-based chemotherapy regimen followed by a lenalidomide (immunomodulatory drug, IMIDs)-based chemotherapy regimen results in better outcomes than conventional treatment. The importance of sufficient reduction of the amyloid precursor protein (free light chain) concentration in the patient's blood by administering a proteasome inhibitor before performing lenalidomide-based regimen was suggested.

Academic Significance and Societal Importance of the Research Achievements

この研究の結果は、ALアミロイドーシス患者のより効果的な化学療法治療計画の策定に役立つ可能性がある。

Research Products

• [Journal Article] Therapeutic Outcome of Lenalidomide-dexamethasone in Patients with Relapsed or Refractory Systemic Immunoglobulin Light Chain (AL) Amyloidosis: A Single-center Analysis and Review of the Literature. (2022)
  • Author(s): Ueno A, Katoh N, Ezawa N, Yoshinaga T, Yazaki M, Sekijima Y.
  • Journal Title: Shinshu Med J Volume: 70 Pages: 29-38
  • Peer Reviewed