Targeting Arginine Shows Promise in Pediatric B-ALL Treatment

August, 08, 2024 | ALL (Acute Lymphoblastic Leukemia), Leukemia

KEY TAKEAWAYS

  • The study aimed to explore metabolic profiles in pediatric B-ALL to enhance treatment strategies during induction chemotherapy.
  • Researchers concluded that Arg increases B-ALL cell sensitivity to standard chemotherapy, offering potential therapeutic benefits.

Precursor B-cell acute lymphoblastic leukemia (B-ALL) is the most common cancer in children. Failure of induction chemotherapy is a significant cause of relapse and mortality in pediatric B-ALL. Altered metabolites are known to play a crucial role in B-ALL carcinogenesis.

Wenqing Wang and the team aimed to investigate the metabolic profiles of children with B-ALL during induction chemotherapy and in various minimal residual disease (MRD) states to improve disease management.

Researchers collected paired peripheral blood plasma samples from children with B-ALL before and after induction chemotherapy, using healthy children as controls. They analyzed the metabolomic profiles of these samples through ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS).

They identified depleted metabolites in children with B-ALL and assessed their concentrations. In vitro, experiments were conducted to examine how these specific metabolites affect the viability of ALL cell lines and their response to standard chemotherapeutic agents.

The result identified 44 metabolites with differing levels between the groups. KEGG pathway enrichment showed that disrupted linoleic acid (LA) metabolism and arginine (Arg) biosynthesis were strongly linked to pediatric B-ALL samples.

Treatment with LA and Arg in pediatric B-ALL samples. Treatment with LA and Arg reduced the viability of NALM-6 and RS4;11 cells in a dose-dependent manner. Additionally, Arg enhanced the sensitivity of B-ALL cells to both L-asparaginase and daunorubicin.

The study concluded that Arg enhances the sensitivity of B-ALL cells to conventional chemotherapeutic drugs like L-asparaginase and daunorubicin, suggesting a potential therapeutic strategy for improving treatment outcomes in pediatric patients with B-ALL.

The study was funded by the Technology and Innovation Commission of Shenzhen Municipality and the Sanming Project of Medicine in Shenzen Municipality.

Source: https://pubmed.ncbi.nlm.nih.gov/39174946/

Wang W, Yu L, Li Z, et al. (2024). “Dysregulated arginine metabolism in precursor B-cell acute lymphoblastic leukemia in children: a metabolomic study.” BMC Pediatr. 2024;24(1):540. Published 2024 Aug 22. doi:10.1186/s12887-024-05015-3

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