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Beyond these direct metabolite-mediated effects, hypoxic niches within the leukemic marrow stabilize HIF-1α in blast populations, driving transcriptional upregulation of PD-L1 and amplifying immune checkpoint-mediated T-cell suppression - while simultaneously feeding back to remodel leukemic cell metabolism by promoting glycolytic flux, suppressing mitochondrial biogenesis, and enhancing OxPhos dependency in residual stem-like populations [29,53]

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