Analysis of ATL progression by CD30 signaling and its biomarkers

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16580
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Nakashima Makoto 東京大学, 大学院新領域創成科学研究科, 特任研究員 (30733232)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: CD30 / CD30シグナル / ATL / 染色体不安定性 / HTLV-1

Outline of Final Research Achievements

We previously reported that a biological link between the expression of CD30, which serves as a marker for ATL progression, and the actively proliferating fraction of HTLV-1-infected cells. To further pursue this finding, we examined whether genomic aberrations are caused by CD30 signaling.
In this study, we found that CD30 signaling induced DNA double-strand breaks (DSBs) via an increase of intracellular reactive oxygen species (ROS) and an accumulation of chromosomal aberrations. Furthermore, CGH analysis revealed that CD30+ATL cells accumulated chromosomal aberrations, focal gains and losses, compared with CD30-ATL cells in ATL individuals.
Taken together these results, accumulation of chromosomal aberrations in patient derived CD30+ATL cells indicates high chromosomal instability, suggesting that CD30 signaling triggers it.

Free Research Field

がん、細胞生物学、分子生物学、腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究結果から、CD30シグナルがATLの病態進展にゲノムレベルで寄与し得ることを示した。したがってCD30は急性型、リンパ腫型などのアグレッシブタイプだけでなく、くすぶり型、慢性型を含む早期癌の段階においても治療標的になり得ることが示唆された。抗CD30抗体医薬であるブレンツキシマブ・ベドチンの有効な投与法開発に資する研究成果であると考えられる。