Elucidation of molecular biology and novel treatment stratgey of malignant lymphomas

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07774
• 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: Okayama University
• Principal Investigator: Ennishi Daisuke 岡山大学, 大学病院, 研究教授 (20825096)
• Co-Investigator(Kenkyū-buntansha): 前田 嘉信 岡山大学, 医歯薬学域, 教授 (60403474)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 悪性リンパ腫 / 遺伝子解析

Outline of Final Research Achievements

DHIT-like lymphoma is a subtype of diffuse large cell lymphomas (DLBCL), which have a gene expression profile characteristic of Double-hit Lymphoma with concurrent MYC and BCL2 translocation, is known as a lymphoma with a very poor prognosis. In this study, we used the argest patient cohort of more than 1000 DLBCL cases in Japan and state-of-the-art gene analysis technology to clarify its molecular mechanism. We identified that the immune escape mechanism and unique cell origin (derived from the germinal center Dark Zone) was a hallmark of molecular profiling of DHIT-like lymphoma. Furthremore, it was revealed that epigenetic genes such as EZH2 and CREBBP are frequently mutated in this subtype, suggesting the theraputic targets of this disease.

Free Research Field

血液腫瘍内科

Academic Significance and Societal Importance of the Research Achievements

造血器腫瘍で最も患者数の多いDLBCLの中で、最近最も予後不良と報告されたDHIT-like lymphomaは、日本人コホートにおいても同様に予後不良である事が確認され、本邦においても早急に治療開発が必要である疾患群であることが改めて認識される結果となった。さらに、本研究における分子病態の解明により、治療標的としてBCL2阻害剤やEZH2阻害剤などのエピゲノム阻害剤の有効性が期待できることが示唆されたことから、今後は臨床開発に向けた基盤整備が要求される。