An investigation of the molecular mechanisms of action of lenalidomide in adult T-cell leukemia (ATL)

• Project/Area Number: 17K14996
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Tokyo Medical University
• Principal Investigator: Yamamoto Junichi 東京医科大学, 医学部, 助教 (40748472)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: がん / 成人T細胞白血病 / IMiDs / 癌

Outline of Final Research Achievements

Lenalidomide, a thalidomide derivative, is approved for adult T-cell leukemia / lymphoma (ATL) in Japan. However, the underlying mechanisms are not clear. In this study, we attempted to identify novel substrates of CRBN, a direct target of lenalidomide, in ATL cell lines. As a result, we identified 12 novel substrates of CRBN that were specifically degraded by treatment of lenalidomide or lenalidomide derivatives in ATL cell line.

Academic Significance and Societal Importance of the Research Achievements

日本には100万人を超えるHTLV-1キャリアが存在し、毎年1000人近くの患者がATLによって亡くなっており、ATLに対する有効な治療法の確立は我が国にとって急務といえる。
本研究でATLに有効な治療薬であるレナリドミドの標的候補が同定されたことによって、その作用機序の解明が進み、より効果的な治療薬の開発に繋がると考えられる。