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2023 Fiscal Year Final Research Report

Analysis of genomic instability through ROS-DSB by CD30 signaling in ATL progression

Research Project

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Project/Area Number 22K15420
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49020:Human pathology-related
Research InstitutionSt. Marianna University School of Medicine (2023)
The University of Tokyo (2022)

Principal Investigator

Nakashima Makoto  聖マリアンナ医科大学, 医学研究科, 助教 (30733232)

Project Period (FY) 2022-04-01 – 2024-03-31
KeywordsCD30 / CD30L / ATL / HTLV-1 / Genomic instability
Outline of Final Research Achievements

Adult T-cell leukemia/lymphoma (ATLL) is a poor prognosis T-cell neoplasm caused by human leukemia virus type I (HTLV-1) infection, which occurs in 3-5% of HTLV-1-infected individuals. I focused on the CD30 molecule, a promising therapeutic target against ATL, to investigate the mechanism of disease progression of ATL. In this study, using clinical samples from patients with ATL, I showed that CD30+ ATL cells stimulated with CD30L induce elevated intracellular ROS, DNA double-strand breaks, and increased chromosomal structural alterations. These results suggest that CD30 signaling induces genomic instability and contributes to the generation of tumor cells with clonal evolution.

Free Research Field

分子生物学、ウイルス学、血液腫瘍学、神経免疫疾患

Academic Significance and Societal Importance of the Research Achievements

CD30シグナルのオンコシグナルとしての実証は、CD30を標的としたATLの早期治療介入および再発を含むATL治療を支持するエビデンスになると考えられる。本研究により得られた結果は、再発ATLに対して寛解実績のある抗CD30抗体薬物複合体 (ブレンツキシマブ・ベドチン)の適切な投薬時期の検討およびCD30のモニタリングを基盤にした革新的診療体制の構築に資するものとなる。CD30シグナルはゲノム変異を惹起する起点シグナルであると考えられ、病態を悪化させるバイオマーカーとして早期に排除すべき細胞であるというコンセプトが示された。

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Published: 2025-01-30  

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