Amiloride-targeted NHE1 undermines leukemia-propagating cells in T-ALL
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A preprint study identifies the sodium-hydrogen exchanger NHE1 as a sustainer of leukemia-propagating capacity and mitochondrial fitness in T-cell acute lymphoblastic leukemia. Screening 786 FDA-approved compounds in a zebrafish transplantation model, the researchers found the diuretic amiloride markedly reduced leukemia-propagating cell frequency without significantly delaying leukemia onset. Mechanistically, NHE1 knockdown cut colony formation in T-ALL cells by more than 70%, while transcriptomic, proteomic and metabolomic analyses pointed to impaired mitochondrial respiration and translation and altered TCA cycle intermediates. In mouse xenografts, leukemia involvement in bone marrow and spleen fell, though overall survival did not differ significantly. The work, posted to bioRxiv in Cancer Biology on October 20, 2026, suggests repurposing potential for amiloride, but the survival question and path to clinical testing remain open.
Written by a model from the reports · updated 1 day ago
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- bioRxivNHE1 sustains leukemia-propagating capacity and mitochondrial fitness in T-cell acute lymphoblastic leukemia
Using a zebrafish transplantation model, the authors screened 786 FDA-approved compounds and found that amiloride markedly reduced the frequency of T-ALL leukemia-initiating cells without significantly delaying disease onset. Mechanistically, NHE1 knockdown reduced colony formation by more than 70% in T-ALL cells; transcriptomic and proteomic analyses showed decreased abundance of proteins involved in mitochondrial respiration and translation, and metabolomics revealed altered TCA cycle intermediates. In mouse xenografts, leukemia involvement in bone marrow and spleen was reduced, but overall survival did not differ significantly.
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