The role of individual HDAC isozymes in refractory cutaneous T-cell lymphomas

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10245
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kochi University
• Principal Investigator: HIGUCHI Tomonori 高知大学, 教育研究部医療学系基礎医学部門, 助教 (00448771)
• Co-Investigator(Kenkyū-buntansha): 橋田 裕美子 高知大学, 教育研究部医療学系基礎医学部門, 助教 (00767999) ; 大畑 雅典 高知大学, 教育研究部医療学系基礎医学部門, 教授 (50263976)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: HDAC4 / ATL

Outline of Final Research Achievements

The current histone deacetylase (HDAC) inhibitors used in the treatment of malignancies are pan-inhibitors with several serious side effects such as thrombocytopenia. Given the relationship between specific HDAC isozymes and different kinds of cancers, we hypothesized isozyme-selective HDAC inhibitors may possess better therapeutic index and fewer adverse effects. In this study, we found that HDAC4 was highly expressed in adult T-cell leukemia/lymphoma (ATL), a refractory cutaneous T-cell lymphoma, and was involved in the proliferation of ATL cells. Furthermore, HDAC4 inhibitor had an anti-tumor effect in ATL cells by inducing a marked increase in apoptosis. Thus, these findings indicate that HDAC4 plays a key role in ATL oncogenesis, and HDAC4 inhibitors might prove to be useful for HDAC-selective therapeutic strategies for refractory cutaneous T-cell lymphoma.

Free Research Field

皮膚腫瘍学

Academic Significance and Societal Importance of the Research Achievements

これまで血液腫瘍で明らかにされていなかったHDAC4の役割として、難治性皮膚T細胞腫瘍であるATLの腫瘍形成に関与することを明らかにし、HDAC4選択的な阻害薬の治療上の有効性についてその可能性を示した。したがって、難治性皮膚T細胞腫瘍において、HDAC4選択的な阻害薬は既存の広域的なHDAC阻害薬の重篤な副作用の問題解決の1つである可能性を有し、これらの成果は個別化医療も視野に入れたHDACアイソザイム選択的な難治性がん治療戦略に関する研究に有用な情報を提供するものである。