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Measurable residual disease analysis in paediatric acute lymphoblastic leukaemia patients with ABL-class fusions. | LitMetric

AI Article Synopsis

  • ABL-class fusions like NUP214-ABL1 and EBF1-PDGFRB are linked to high-risk acute lymphoblastic leukaemia (ALL), and the study aims to assess new DNA-based tests for measurable residual disease (MRD) compared to traditional Ig/TCR markers.
  • Researchers implemented targeted genomic sequencing and quantitative PCR assays on bone marrow samples to analyze MRD while adhering to EuroMRD guidelines.
  • The results showed that DNA-based fusion tests had high accuracy in tracking MRD for ABL-class fusions and IKZF1-deletions, outperforming Ig/TCR tests, especially in BCR-ABL1 patients where discordance rates were significantly higher.

Article Abstract

Background: ABL-class fusions including NUP214-ABL1 and EBF1-PDGFRB occur in high risk acute lymphoblastic leukaemia (ALL) with gene expression patterns similar to BCR-ABL-positive ALL. Our aim was to evaluate new DNA-based measurable residual disease (MRD) tests detecting these fusions and IKZF1-deletions in comparison with conventional immunoglobulin/T-cell receptor (Ig/TCR) markers.

Methods: Precise genomic breakpoints were defined from targeted or whole genome next generation sequencing for ABL-fusions and BCR-ABL1. Quantitative PCR assays were designed and used to re-measure MRD in remission bone marrow samples previously tested using Ig/TCR markers. All MRD testing complied with EuroMRD guidelines.

Results: ABL-class patients had 46% 5year event-free survival and 79% 5year overall survival. All had sensitive fusion tests giving high concordance between Ig/TCR and ABL-class fusion results (21 patients, n = 257 samples, r2 = 0.9786, P < 0.0001) and Ig/TCR and IKZF1-deletion results (9 patients, n = 143 samples, r2 = 0.9661, P < 0.0001). In contrast, in BCR-ABL1 patients, Ig/TCR and BCR-ABL1 tests were discordant in 32% (40 patients, n = 346 samples, r2 = 0.4703, P < 0.0001) and IKZF1-deletion results were closer to Ig/TCR (25 patients, n = 176, r2 = 0.8631, P < 0.0001).

Conclusions: MRD monitoring based on patient-specific assays detecting gene fusions or recurrent assays for IKZF1-deletions is feasible and provides good alternatives to Ig/TCR tests to monitor MRD in ABL-class ALL.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9427854PMC
http://dx.doi.org/10.1038/s41416-022-01806-6DOI Listing

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