Prediction of the onset of treatment-related myeloproliferative neoplasms after treatment for malignant lymphoma by genetic analysis of bone marrow cell

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16811
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Tokyo Medical University
• Principal Investigator: Katagiri Seiichiro 東京医科大学, 医学部, 助教 (50532298)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 悪性リンパ腫 / 治療関連骨髄腫瘍 / クローン性造血

Outline of Final Research Achievements

In this study, we used next-generation sequencing technology to perform targeted deep sequencing only at specific sites and analyze clonal hematopoies in the bone marrow at the time of diagnosis of malignant lymphoma. The purpose was to predict the potential risk of developing therapy-related myeloid neoplasm (t-MN). For patients who developed t-MN after treatment for malignant lymphoma, we conducted a molecular analysis using myeloid targeted deep sequencing in pre-treatment and tMN BM samples. 80% of tMN patients showed clonal hematopoiesis in the BM before chemotherapy for ML. Furthermore, none of the major clones of clonal hematopoies found at the onset of malignant lymphoma had a common clone with t-MN that developed thereafter. From this result, it was considered that the existence of clonal hematopoies before chemotherapy may indicate the possibility of clonal instability that facilitates the emergence of new clones by chemotherapy.

Free Research Field

血液内科学分野

Academic Significance and Societal Importance of the Research Achievements

悪性リンパ腫は治療関連骨髄性腫瘍の一次腫瘍として大きな割合を占めている。これまで悪性リンパ腫診断時の骨髄検体を用いて、t-MN発症を予測した研究は報告されておらず、本研究は悪性リンパ腫診断時の骨髄検体を用いてクローン性造血を評価することで、治療後のt-MN発症リスクの評価ができる可能性を示した。将来的に悪性リンパ腫治療後の二次発癌の可能性まで考慮した治療戦略が作られてることが期待される。