Frequency and prognostic impact of ZEB2 H1038 and 1072 mutations in childhood B-other acute lymphoblastic leukemia
Abstract
In this study, we aimed to determine the frequency and clinical relevance of ZEB2mut in childhood B-other ALL. Using WES, RNAseq and amplicon sequencing of DNA or cDNA, we analyzed 231 and 36 Czech children with newly manifesting and relapsed B-other ALL, respectively (= "discovery cohorts"), consecutively diagnosed between November 2002 and December 2017 and treated according to several successive BFM-based protocols (see Supplementary Data).
We detected ZEB2mut in 3.8% (9/231) of newly diagnosed B-other ALL. ZEB2mut was associated with significantly worse event-free survival and higher relapse (Figure 1A,B).
In accord with the higher relapse rate, we found significant enrichment of ZEB2mut in relapse cohort (8/36, 29%; P=0.0005). Interestingly, 2 out of total 9 relapses were isolated extramedullary, plus one combined.