RNA-sequencing: A reliable tool to unveil transcriptional landscape of paediatric B-other acute lymphoblastic leukaemia

Abstract

B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) comprises multiple subtypes characterized by different genetic alterations. With the use of current standard-of-care tests used in clinical practice, 20%–30% of the cases may not be classified into the main genetic subtypes and additional approaches are needed. These patients are grouped in the heterogeneous category B-other ALL. Transcriptome sequencing (RNA-seq) has allowed the identification of novel fusion genes and gene expression profiles that define new molecular subtypes. We present RNA-seq results integrated, in a real-world scenario, with clinical routine diagnostic data to identify new biomarkers and reclassify a cohort of 60 B-other ALL patients in the newly described genetic subtypes. Overall, 49 rearrangements were identified, including 32 different fusion genes in 41 B-other patients (68%). Moreover, we reported six novel rearrangements (IGK::PAX5, PAX5::IL1RAPL1, ETV6::KRT78, IGH::HIC1, IGH::MIR100HG and NKAIN4::PNPLA7). The integration of RNA-seq results with standard-of-care data allowed us to classify 72% of the patients (43/60) in 11 different subtypes, being DUX4 rearranged and PAX5alt the most represented subtypes. In summary, RNA-seq is a reliable tool for the identification of new emerging genetic subtypes contributing to a better genetic risk stratification of BCP-ALL paediatric patients on the path towards a more personalized medicine.