Exploration of a novel mechanism of glycolysis enhancement in B-cell tumors and investigation of its usefulness as a therapeutic target

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17854
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: National Hospital Organization Nagoya Medical Center
• Principal Investigator: Imahashi Nobuhiko 独立行政法人国立病院機構(名古屋医療センター臨床研究センター), その他部局等, 血液内科医師 (90726861)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: B細胞性腫瘍 / 代謝

Outline of Final Research Achievements

In this study, we investigated the possibility that the metabolism of B-cell malignancies is activated by T cells, which leads to the treatment resistance of B-cell malignancies. The results of glucose uptake assay suggested that glycolysis of chronic lymphocytic leukemia cells is activated by T cells. Moreover, survival of chronic lymphocytic leukemia cells was supported by T cells. However, the increased glycolytic activity of chronic lymphocytic leukemia cells by T cells was unlikely to be involved in the enhanced survival of leukemia cells. We did not observe a clear increase in glucose uptake by T cells in other B-cell tumors. However, we found that survival of myeloma cell lines was supported by T cells. These results may pave a way to development of novel therapy for B-cell tumors.

Free Research Field

B細胞性腫瘍

Academic Significance and Societal Importance of the Research Achievements

B細胞性腫瘍の解糖系亢進が、B細胞性腫瘍の治療成績低下の一因になっていることが明らかになっている。これまでの研究では、B細胞性腫瘍の解糖系が亢進する機序としては、癌関連遺伝子の異常などが報告されているが、本研究では、B細胞性腫瘍の代謝がT細胞により活性化されるという全く新しい仮説を検証し、慢性リンパ性白血病において、その可能性があることを明らかにした。また、多発性骨髄腫の生存がT細胞により支持されていることを示唆する知見もえられた。これらの知見は、B細胞性腫瘍に対する新規治療法の開発につながる可能性がある。