IL21-STAT3 controls the pentose phosphate pathway to support metabolic reprogramming and tumor progression in chronic lymphocytic leukemia.

ABSTRACT: Studying how microenvironmental cues influence metabolic reprogramming can uncover mechanisms driving tumor progression. Using an in vitro model with proliferative stimuli of the in vivo lymph node niche (LN)-including interleukin-21 (IL-21)-we examined metabolic rewiring in chronic lymphocytic leukemia (CLL) cells. We found that the metabolic intermediates of upper glycolysis and its branching pathways are key in fulfilling metabolic demands of proliferating CLL cells. Among branching pathways, the pentose phosphate pathway (PPP) was the most transcriptionally upregulated in proliferating CLL cells. Increased expression of PPP genes was detected ex vivo at the bulk and single-cell level in the LN-resident and -emigrating CLL cells, with more consistency across enzymes of the nonoxidative

SUBMITTER: Del Prete R 

PROVIDER: S-EPMC12836863 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature