Genomic fusion breakpoints for MRD monitoring in pediatric ALL

Results from a large single-center study, evaluating genomic fusion breakpoint (GFB)-based measurable residual disease (MRD) monitoring in pediatric acute lymphoblastic leukemia (ALL), were published in Leukemia by Houtman et al. Genomic fusions were identified in 403 patients; GFB-MRD was benchmarked against gold-standard immunoglobulin/T-cell receptor (IG/TCR)-based assays for MRD monitoring in 104 patients in whom both tests were performed in parallel on follow-up samples.

Key data: Patient-specific GFBs were identified in 97% of cases, with no fusions detected among negative ALL controls. Quantitative polymerase chain reaction (qPCR) assays were successful in 98% of selected ALL patients (n = 167), with the sensitivity range (SR) of 10⁻⁴ reached in 98% and the quantification range (QR) of 10⁻⁴ reached in 65%. In 104 patients, compared with IG/TCR-based assays, GFB-MRD showed comparable SR (≤10⁻⁴; 97% vs 98%) but higher QR (≤10⁻⁴; 68% vs 52%; χ² p = 0.021). GFB assays also demonstrated superior specificity in healthy peripheral blood lymphocyte (PBL) controls, with 1/104 GFB markers showing nonspecific amplification compared with 92/215 IG/TCR markers (χ² p = 1.3 × 10⁻¹⁴). Among 453 paired samples, 76% of MRD results were concordant between marker types; GFB-MRD resolved IG/TCR gray-zone results and remained informative regardless of marker evolution or oligoclonality, particularly for ETV6::RUNX1- and MEF2D-rearranged ALL. Overall correlation between MRD values was strong (R² = 0.76), improving to R² = 0.87 when BCR::ABL1-positive cases were excluded.

Key learning: GFB-based MRD monitoring provides a complementary approach to IG/TCR-based MRD in pediatric fusion-driven ALL, with potential utility in subgroups where conventional markers may be compromised.