ArticleCell death & disease2024
Histidine re-sensitizes pediatric acute lymphoblastic leukemia to 6-mercaptopurine through tetrahydrofolate consumption and SIRT5-mediated desuccinylation.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 2 citations in OpenAlex.
- Histidine to glutamine substitutants, a regulated process that impacts cell survival and suggests histidine shortage in cancer.Cell death discovery · 2026Article
- Preparation and Properties ofInternational journal of food science · 2026Article
- Succinylation in cancer immunotherapy: mechanisms, biomarkers, and therapeutic implications.Frontiers in immunology · 2026Review
- The integrated analysis of SIRT family expression, prognostic value, and potential implications in childhood acute lymphoblastic leukemia.Frontiers in oncology · 2025Article
- Mitochondrial Sirtuins in Cancer: A Revisited Review from Molecular Mechanisms to Therapeutic Strategies.Theranostics · 2024Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
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Abstract
Despite progressive improvements in the survival rate of pediatric B-cell lineage acute lymphoblastic leukemia (B-ALL), chemoresistance-induced disease progression and recurrence still occur with poor prognosis, thus highlighting the urgent need to eradicate drug resistance in B-ALL. The 6-mercaptopurine (6-MP) is the backbone of ALL combination chemotherapy, and resistance to it is crucially related to relapse. The present study couples chemoresistance in pediatric B-ALL with histidine metabolism deficiency. Evidence was provided that histidine supplementation significantly shifts the 6-MP dose-response in 6-MP-resistant B-ALL. It is revealed that increased tetrahydrofolate consumption via histidine catabolism partially explains the re-sensitization ability of histidine. More importantly, this work provides fresh insights into that desuccinylation mediated by SIRT5 is an indispensable and synergistic requirement for histidine combination therapy against 6-MP resistance, which is undisclosed previously and demonstrates a rational strategy to ameliorate chemoresistance and protect pediatric patients with B-ALL from disease progression or relapse.
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