New glycolytic activation mechanism in leukemic cells during glucose starvation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08735
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Hokkaido University (2022); University of Miyazaki (2020-2021)
• Principal Investigator: Saito Yusuke 北海道大学, 医学研究院, 客員研究員 (20585674)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 白血病 / 解糖系 / マンノース

Outline of Final Research Achievements

Because leukemia cells proliferate by consuming glucose as an energy source, an alternative nutrient source is essential when glucose levels in bone marrow are insufficient. We profiled sugar metabolism in leukemia cells and found that mannose is an energy source for glycolysis, the tricarboxylic acid (TCA) cycle. Leukemia cells express high levels of phosphomannose isomerase (PMI), which mobilizes mannose to glycolysis; consequently, even mannose in the blood can be used as an energy source for glycolysis. Conversely, suppression of PMI expression or a mannose load exceeding the processing capacity of PMI inhibited transcription of genes related to mitochondrial metabolism and TCA cycle, thus suppressing the growth of leukemia cells. Our findings reveal a new mechanism for glucose starvation resistance in leukemia.

Free Research Field

がん代謝

Academic Significance and Societal Importance of the Research Achievements

本研究は白血病細胞が糖質飢餓状態において代替糖質を利用することで生存することを証明した。これまで解糖系を標的とした治療薬は臨床応用には至っておらず、PMI阻害剤の開発やマンノースの過剰投与が白血病細胞のエネルギーを枯渇させる新規治療として期待される。