Genetic dissection of molecular mechanisms in ATL

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H06249
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: National Cancer Center Japan (2017-2018); Kyoto University (2016)
• Principal Investigator: Keisuke Kataoka 国立研究開発法人国立がん研究センター, 研究所, 分野長 (90631383)
• Research Collaborator: Shimoda Kazuya
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 癌 / 成人T細胞白血病リンパ腫 / 遺伝学

Outline of Final Research Achievements

We investigated the association between genetic alterations and disease status in ATL. We found that TP53 and IRF4 mutations as well as numerous copy number alterations were associated with aggressive ATL (acute and lymphoma subtypes). By contrast, STAT3 mutations were related to chronic and smoldering subtypes. In addition, we analyzed the effect of genetic alterations on patient survival. We found that a set of genetic alterations, particularly PD-L1 copy number amplifications, were associated with worse prognosis even when established clinical prognostic factors were adjusted.
We also developed a novel transgenic mouse model harboring the PRKCB D427 mutation. We analyzed this model, but found no phenotype in the immune and hematopoietic systems.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、臨床的因子と独立して予後不良と関連する遺伝子異常を同定することが出来た。この結果、臨床的な重要性に基づいた上で治療標的として有用な遺伝子異常が同定されたことのみならず、ATLにおける遺伝子異常のバイオマーカー(予後因子)として有用性が解明され、治療方針の決定に役立つ予後予測モデルの確立に繋がることが期待される。