ArticleHemaSphere2026
IL21-STAT3 controls the pentose phosphate pathway to support metabolic reprogramming and tumor progression in chronic lymphocytic leukemia.
Article in HemaSphere, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
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 PPP branch. Expression of the latter correlated with shorter failure-free survival in CLL patients. At the cellular level, metabolomics and 13C-glucose tracing confirmed high activity of the non-oxidative PPP in proliferating CLL cells. IL-21 regulated the expression of PPP enzymes, with STAT3 serving as the primary downstream effector. CRISPR/Cas9-mediated silencing of PPP enzymes revealed that, in vitro, proliferating CLL cells from most patients were not dependent on these enzymes. In contrast, silencing transketolase (TKT)-the rate-limiting enzyme of the non-oxidative PPP-abolished tumor engraftment in vivo, demonstrating that CLL cells rely on this pathway within the tumor microenvironment. These findings uncover a CLL-specific metabolic reprogramming wherein IL-21-STAT3 drives PPP activity and identify the nonoxidative PPP as a critical in vivo vulnerability of leukemic cells in the murine CLL model.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.