Crosstalk between Glycolysis and NF-kappa B activation in malignant lymphoma cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K17826
• 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: University of Yamanashi
• Principal Investigator: Nakajima Kei 山梨大学, 大学院総合研究部, 臨床助教 (20447709)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 悪性リンパ腫 / 解糖系 / ヘキソキナーゼ２ / NF-κB / AMPK

Outline of Final Research Achievements

In B-cell lymphoma cell lines, c-MYC and NF-κB-p65 phosphorylation induced Hexokinase2:HK2 expression by HIF1 and resistance to anticancer drugs.and we focused on AMPK to prove the positive feedback mechanism between HK2 expression and NF-κB-p65 phosphorylation. Inhibition of glycolysis by low glucose medium and metformin(Biguanide antidiabetic) caused phosphorylation of AMPK, and metformin caused deacetylation (acetyl K310) of NF-κB followed by dephosphorylation (p65 Ser536), suggesting a positive feedback mechanism initiated by AMPK phosphorylation.

Free Research Field

血液学

Academic Significance and Societal Importance of the Research Achievements

再発難治の悪性リンパ腫では近年新規治療薬や移植細胞治療により治療成績は改善してきているが薬剤が高額であったり、地理的な問題で治療施設へのアクセスが限られてしまう場合もある。既存の薬剤の組み合わせ等で解糖系による抗がん剤耐性を解除することができれば、難治患者においても治療成績を向上させることができると考えられる。