Histidine re-sensitizes acute lymphoblastic leukemia cells to 6-mercaptopurine through tetrahydrofolate consumption and SIRT5-mediated desuccinylation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA993153 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25223537_1.fastq.gz | Fastqsanger.gz | |||
| SRR25223537_2.fastq.gz | Fastqsanger.gz | |||
| SRR25223538_1.fastq.gz | Fastqsanger.gz | |||
| SRR25223538_2.fastq.gz | Fastqsanger.gz | |||
| SRR25223539_1.fastq.gz | Fastqsanger.gz |
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Project description: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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