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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 harboringPAX5 orCRLF2 fusions (G9),PAX5 (p.P80R) mutations (G10),IKZF1 (p.N159Y) mutations (G11), eitherZEB2 (p.H1038R) mutations orIGH–CEBPE fusions (G12),HLF rearrangements (G13), orNUTM 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.

Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases