A RECENT study has demonstrated how RNA sequencing (RNA-seq) can enhance the genetic classification of B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) patients, leading to better risk stratification and paving the way for more personalised treatment approaches.
BCP-ALL is a type of leukaemia with various subtypes defined by different genetic alterations. However, current diagnostic tests fail to classify 20%-30% of cases, leaving them grouped under the ambiguous “B-other ALL” category. This lack of classification can hinder optimal treatment strategies. The study integrated RNA-seq with routine clinical diagnostic data, allowing researchers to identify new fusion genes and gene expression profiles that define novel molecular subtypes of BCP-ALL.
In a cohort of 60 B-other ALL patients, the research uncovered 49 rearrangements, including 32 distinct fusion genes in 41 patients (68%). Six of these rearrangements were previously unknown, such as IGK::PAX5 and PAX5::IL1RAPL1. The integration of RNA-seq results enabled the classification of 72% of patients into 11 different subtypes, with DUX4 rearranged and PAX5 alterations being the most prevalent.
These findings highlight RNA-seq as a powerful tool for identifying emerging genetic subtypes of BCP-ALL, offering new insights for more precise genetic risk stratification. This approach brings us closer to tailoring treatment to the unique genetic makeup of each patient, contributing to a more personalised medicine strategy for paediatric BCP-ALL.
Helena Bradbury, EMJ
Reference
Vicente-Garces C et al. RNA-sequencing: A reliable tool to unveil transcriptional landscape of paediatric B-other acute lymphoblastic leukaemia. BJ Haem. 2025; https://doi.org/10.1111/bjh.20056.
