ArticleBlood2026
Guanine nucleotides drive ribosome biogenesis and glycolytic reprogramming in acute myeloid leukemia stem cells.
Article in Blood, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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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.
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Who cites it
1 citing paper in PubMed.
- Association of DNA damage response gene polymorphisms with treatment response and prognosis in acute myeloid leukemia.Journal of Cancer · 2026Article
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16 authors.
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No grant is acknowledged in the PubMed record.
Abstract
abstractTherapy resistance in acute myeloid leukemia (AML) remains a major clinical obstacle, particularly because of the persistence of leukemia stem cells (LSC) capable of metabolic adaptation. Although venetoclax (Ven) inhibits oxidative phosphorylation (OXPHOS), we found that Ven-resistant LSC undergo glycolytic reprogramming to bypass OXPHOS inhibition. This metabolic shift is supported by enhanced ribosome biogenesis, which is sustained by upregulated de novo guanine nucleotide biosynthesis. Abundant guanine nucleotides suppress the impaired ribosome biogenesis checkpoint (IRBC), leading to TP53 destabilization and persistent MYC expression. The inhibition of inosine monophosphate dehydrogenases (IMPDH1/2) depletes guanine nucleotides, activates IRBC, stabilizes TP53, represses MYC, and impairs the metabolic shift to glycolysis. This metabolic rewiring disrupts LSC stemness and suppresses the reconstitution of human AML cells in xenotransplantation experiments. Notably, the suppression of LSC stemness was observed regardless of Ven resistance or the TP53 mutational status of AML cells. These findings reveal that mutation-independent TP53 inactivation is involved in resistant AML and suggest that targeting guanine nucleotide biosynthesis may offer a clinically actionable strategy to eradicate therapy-resistant LSC.
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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 Socratic graph.