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Background <p>The molecular characterisation of pediatric acute lymphoblastic leukemia (pALL) is essential for accurate diagnosis and risk stratification. However, standard-of-care (SoC) methods have limited sensitivity and resolution.</p> Methods <p>This study evaluates the clinical utility of emerging genomic technologies—including optical genome mapping (OGM), digital multiplex ligation-dependent probe amplification (dMLPA), RNA sequencing (RNA-seq), and targeted next-generation sequencing (t-NGS)—in the largest cohort of pALL patients analysed to date, with 60 cases using OGM.</p> Results <p>Considering clinically relevant alterations identified with at least two different methods, OGM as a standalone test demonstrated superior resolution, detecting chromosomal gains and losses (51.7% vs. 35%, <i>p</i> = 0.0973) and gene fusions (56.7% vs. 30%, <i>p</i> = 0.0057), while resolving 15% of non-informative cases. Combining dMLPA and RNA-seq was the most effective approach, achieving precise classification of complex subtypes and uniquely identifying IGH rearrangements undetected by other techniques. OGM identified clinically relevant alterations in 90% of cases, and the dMLPA-RNAseq combination reached 95%, compared to 46.7% with SoC techniques.</p> Conclusions <p>Integrating these technologies into diagnostic workflows overcomes SoC limitations. OGM and the dMLPA-RNAseq combination emerge as front-line strategies, addressing pALL heterogeneity, streamlining molecular testing, and informing treatment decisions to improve outcomes.</p>

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Benchmarking standard-of-care and emerging genomic approaches to enhance diagnosis in pediatric acute lymphoblastic leukemia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月30日

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  • José Vicente Gil,
  • Gayane Avetisyan,
  • Alberto Miralles,
  • Sandra de las Heras,
  • Álvaro Díaz-González,
  • Carolina López-Benet,
  • María del Cañizo,
  • Ana Vicente,
  • Rafael Andreu,
  • Carolina Fuentes,
  • José María Fernández,
  • Eva Barragán,
  • Esperanza Such,
  • Marta Llop

摘要

Background

The molecular characterisation of pediatric acute lymphoblastic leukemia (pALL) is essential for accurate diagnosis and risk stratification. However, standard-of-care (SoC) methods have limited sensitivity and resolution.

Methods

This study evaluates the clinical utility of emerging genomic technologies—including optical genome mapping (OGM), digital multiplex ligation-dependent probe amplification (dMLPA), RNA sequencing (RNA-seq), and targeted next-generation sequencing (t-NGS)—in the largest cohort of pALL patients analysed to date, with 60 cases using OGM.

Results

Considering clinically relevant alterations identified with at least two different methods, OGM as a standalone test demonstrated superior resolution, detecting chromosomal gains and losses (51.7% vs. 35%, p = 0.0973) and gene fusions (56.7% vs. 30%, p = 0.0057), while resolving 15% of non-informative cases. Combining dMLPA and RNA-seq was the most effective approach, achieving precise classification of complex subtypes and uniquely identifying IGH rearrangements undetected by other techniques. OGM identified clinically relevant alterations in 90% of cases, and the dMLPA-RNAseq combination reached 95%, compared to 46.7% with SoC techniques.

Conclusions

Integrating these technologies into diagnostic workflows overcomes SoC limitations. OGM and the dMLPA-RNAseq combination emerge as front-line strategies, addressing pALL heterogeneity, streamlining molecular testing, and informing treatment decisions to improve outcomes.