2026-04-13T14:26:20Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1943062025-11-19T20:41:33Zcom_2072_1057col_2072_478781col_2072_478917

00925njm 22002777a 4500 dc Baptista, Inês do Carmo Viegas author Karakitsou, Effrosyni author Cazier, Jean-Baptiste author Günther, Ulrich L. author Marín Martínez, Silvia author Cascante i Serratosa, Marta author 2023-02-28T09:04:24Z 2023-02-28T09:04:24Z 2022-03-25 2023-02-28T09:04:24Z Increased expression of transketolase (TKT) and its isoform transketolase-like-1 (TKTL1) has been related to the malignant leukemia phenotype through promoting an increase in the non-oxidative branch of the pentose phosphate pathway (PPP). Recently, it has also been described that TKTL1 can have a role in survival under hypoxic conditions and in the acquisition of radio resistance. However, TKTL1's role in triggering metabolic reprogramming under hypoxia in leukemia cells has never been characterized. Using THP-1 AML cells, and by combining metabolomics and transcriptomics techniques, we characterized the impact of TKTL1 knockdown on the metabolic reprogramming triggered by hypoxia. Results demonstrated that TKTL1 knockdown results in a decrease in TKT, glucose-6-phosphate dehydrogenase (G6PD) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activities and impairs the hypoxia-induced overexpression of G6PD and GAPDH, all having significant impacts on the redox capacity of NADPH- and NADH-related cells. Moreover, TKTL1 knockdown impedes hypoxia-induced transcription of genes encoding key enzymes and transporters involved in glucose, PPP and amino acid metabolism, rendering cells unable to switch to enhanced glycolysis under hypoxia. Altogether, our results show that TKTL1 plays a key role in the metabolic adaptation to hypoxia in THP-1 AML cells through modulation of G6PD and GAPDH activities, both regulating glucose/glutamine consumption and the transcriptomic overexpression of key players of PPP, glucose and amino acids metabolism. Metabolisme Cicle de la pentosa-fosfat Leucèmia Enzims Metabolism Pentose phosphate pathway Leukemia Enzymes TKTL1 Knockdown Impairs Hypoxia-Induced Glucose-6-phosphate Dehydrogenase and Glyceraldehyde-3-phosphate Dehydrogenase Overexpression