A RECENT study has shed light on the genomic factors contributing to relapse in children with acute lymphoblastic leukaemia (ALL), the most common childhood tumour and leading cause of death in children. While many studies have focused on high-risk ALL, standard-risk (SR) ALL, which accounts for almost half of ALL relapsed cases, has largely been neglected.
The team conducted extensive genome and transcriptome sequencing on diagnostic and remission samples from 1,381 children with SR ALL and 115 with high-risk B-cell ALL with favourable cytogenetic features, enrolled across four Children’s Oncology Group clinical trials. The authors aimed to identify the genomic determinants of relapse by comparing 439 patients who experienced relapse with 1,057 patients who remained in complete remission for at least 5 years.
The findings revealed that specific genomic subtypes were closely associated with relapse risk. Notably, children with PAX5-altered ALL had a significantly higher likelihood of relapse, with approximately 50% of cases resulting in relapse (odds ratio [OR]: 3.31 [95% CI: 2.17–5.03]; P=3.18×10–8). Additionally, within the high-hyperdiploid ALL subgroup, certain chromosomal patterns were linked to patient outcomes. For instance, gain of chromosome 10 combined with disomy of chromosome 7 was associated with a favourable outcome (OR: 0.27 [95% CI: 0.17–0.42]; P=8.02×10–10), while disomy of chromosomes 10 and 17 along with a gain of chromosome 6 was linked to a much higher relapse risk (OR: 7.16 [95% CI: 2.63–21.51]; P=2.19×10–5).
Further analysis identified secondary genomic alterations, such as changes in INO80, IKZF1, and CREBBP genes, that were also associated with relapse in a subtype-dependent manner.
The authors concluded that comprehensive genomic analysis is crucial for optimal risk stratification in childhood ALL. By identifying specific genetic markers linked to relapse, this research could pave the way for more personalised and effective treatment strategies for children with ALL.
Ada Enesco, EMJ
Reference
Chang TC et al. Genomic determinants of outcome in acute lymphoblastic leukemia. J Clin Oncol. 2024; DOI:10.1200/JCO.23.02238.
