The impact of asparaginase phenotype-related single nucleotide polymorphisms on prognosis in pediatric B-cell...

Pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a significant hematological malignancy and asparaginase plays a significant role in the treatment of BCP-ALL. However, the prognostic value of asparaginase phenotype-related single nucleotide polymorphisms (SNPs) in BCP-ALL remains unclear.

Here, we examined clinical characteristics, genetic mutations, asparaginase phenotype-related SNPs (ADSL (793-49A > C), NFATC2 (2722 + 12367 T > A), PNPLA3 (444C > G), and SOD2 (47A > G)) and treatment outcomes in a retrospective cohort of 356 newly diagnosed BCP-ALL patients.

Kaplan-Meier survival analysis of relapse-free survival (RFS) identified five significant risk factors: age ≥ 10 years, white blood cell count ≥ 50 × 10⁹/L, minimal residual disease (MRD) ≥ 1.0% at Day 15, MRD ≥ 0.01% at Day 33, and the ADSL (793-49A > C) AC/CC genotype (all P < 0.05). Notably, multivariate Cox regression analysis confirmed MRD ≥ 1.0% at Day 15, NF1 mutations, and the ADSL (793-49A > C) AC/CC genotype as independent poor prognostic factors for RFS. Differences in clinical characteristics between ADSL (793-49A > C) variant and wild genotypes were observed, revealing higher proportion of females, steroid non-responder and MRD ≥ 1.0% at Day 15 in the variant group.

These findings underscore the importance of asparaginase phenotype-related SNP, ADSL (793-49A > C), in personalized treatment strategies based on genetic profiling and clinical parameters, potentially enhancing therapeutic efficacy and patient outcomes in pediatric BCP-ALL.