AI Article Synopsis
- * The study investigates the relationship between chemoresistance in B-ALL and histidine metabolism, revealing that histidine supplementation can improve responsiveness to the standard chemotherapy drug, 6-mercaptopurine (6-MP).
- * It highlights the importance of desuccinylation by the enzyme SIRT5 as a crucial factor in enhancing the effectiveness of histidine therapy, offering a new strategy to combat chemoresistance and improve survival rates in young B-ALL patients.
Article 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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10940622 | PMC |
| http://dx.doi.org/10.1038/s41419-024-06599-5 | DOI Listing |
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