Expression of genes involved in glycolytic pathway upon glucose limitation in leukemia cells

Abstract

Objective: Leukemia is the cancer of hematopoietic system and is characterized by abnormal proliferation of blood precursor cells. Leukemia cells as other cancer cells multiply rapidly and they have increased nutrient needs. The most commonly used nutrient by cancer cells is glucose and therefore it is hypothesized that glucose is present at a low level in the microenvironment of cancer cells. Metabolic changes in leukemia cells due to nutrient deficiency add extra liabilities to the cells. In recent studies, increased glycolysis and reprogrammed glucose metabolism have been shown in different tumors Intermediate steps of glycolysis involving hexokinase, phosphofructokinase, pyruvate dehydrogenase kinase and lactate dehydrogenase enzymes are rate-limiting steps in the reaction and increased expressions were correlated with poor prognosis of leukemia.The aim of this study is to investigate the expression of glycolytic genes in low glucose conditions. Method: In this study, we control expression of rate-limiting glycolytic enzymes’ mRNA expressions in K562, NB-4 and HL-60 cell lines in low glucose (1 mM) concentration compared to normal (10 mM) concentration using qRT-PCR assay. Results: We found that PKM2 and LDHA mRNA expressions were significantly decreased in low glucose conditions. On the other hand, HK1 and HK2 expressions were increased in K562 cells (p<0.001). We also found that PFKL expression was decreased in K562 cells. Conclusion: Our results show that targeting glucose metabolism can reduce expression of glycolytic genes and therefore in compliance with the literature suggest that glucose metabolism may be a target in the treatment of leukemia. © Istanbul Medeniyet University Faculty of Medicine.