Abstract

Significance In BCP ALL, molecular classification is used for risk stratification and influences treatment strategies. We reanalyzed the transcriptomic landscape of 1,223 BCP ALLs and identified 14 subgroups based on their transcriptional profiles. Eight of these (G1 to G8) are previously well-known subgroups, harboring specific genetic abnormalities. The sample size allowed the identification of six previously undescribed subgroups, consisting of cases harboring PAX5 or CRLF2 fusions (G9), PAX5 (p.P80R) mutations (G10), IKZF1 (p.N159Y) mutations (G11), either ZEB2 (p.H1038R) mutations or IGH–CEBPE fusions (G12), HLF rearrangements (G13), or NUTM rearrangements (G14). In addition, this study allowed us to determine the prognostic impact of several recently defined subgroups. This study suggests that RNA sequencing should be a valuable tool in the routine diagnostic workup for ALL.