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Background <p>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.</p> Methods <p>Here, we examined clinical characteristics, genetic mutations, asparaginase phenotype-related SNPs (<i>ADSL</i> (793-49A &gt; C), <i>NFATC2</i> (2722 + 12367&#xa0;T &gt; A), <i>PNPLA3</i> (444C &gt; G), and <i>SOD2</i> (47A &gt; G)) and treatment outcomes in a retrospective cohort of 356 newly diagnosed BCP-ALL patients.</p> Results <p>Kaplan–Meier survival analysis of relapse-free survival (RFS) identified five significant risk factors: age ≥ 10&#xa0;years, white blood cell count ≥ 50 × 10<sup>9</sup>/L, minimal residual disease (MRD) ≥ 1.0% at Day 15, MRD ≥ 0.01% at Day 33, and the <i>ADSL</i> (793-49A &gt; C) AC/CC genotype (all <i>P</i> &lt; 0.05). Notably, multivariate Cox regression analysis confirmed MRD ≥ 1.0% at Day 15, <i>NF1</i> mutations, and the <i>ADSL</i> (793-49A &gt; C) AC/CC genotype as independent poor prognostic factors for RFS. Differences in clinical characteristics between <i>ADSL</i> (793-49A &gt; 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.</p> Conclusions <p>These findings underscore the importance of asparaginase phenotype-related SNP, <i>ADSL</i> (793-49A &gt; C), in personalized treatment strategies based on genetic profiling and clinical parameters, potentially enhancing therapeutic efficacy and patient outcomes in pediatric BCP-ALL.</p>

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The impact of asparaginase phenotype-related single nucleotide polymorphisms on prognosis in pediatric B-cell precursor acute lymphoblastic leukemia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月6日

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  • Jingying Zhang,
  • Caiting Xu,
  • Jiayue Qin,
  • Diying Shen,
  • Lixia Liu,
  • Tian Xia,
  • Xiaojun Xu

摘要

Background

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.

Methods

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.

Results

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.

Conclusions

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.