Postnatal origin of the chromosomal gains in older patients with high hyperdiploid acute lymphoblastic leukemia

Abstract

We show that there is a marked difference in the percentage of BTRI/all SNVsbetween young children and older children, adolescents, and adults in HeH ALL. We interpret this asmost HeH ALL occurring in patients <10 years at diagnosis, constituting the majority of cases, have aprenatal origin of the chromosomal gains, in line with previous findings.4-13 In contrast, HeH ALLoccurring in older children, adolescents, and adults generally have a later, most likely postnatal,origin of the chromosomal gains. Notably, some cases in young children may also fall into this group,suggesting a hitherto unknown heterogeneity within HeH ALL. Considering that we have recentlyshown that the chromosomal gains occur simultaneously and very early in the leukemogenesis ofHeH ALL,15 we deem it likely that this means that also the ALL arises postnatally in these cases,although we cannot definitely exclude another, as yet hidden, primary event.