Two novel cases of NUTM1-rearranged B-cell acute lymphoblastic leukaemia presenting with high-risk features

Abstract

Rare recurrent chromosomal rearrangements involving15q13–15 have been reported in paediatric B-cell acute lym-phoblastic leukaemia (B-ALL), occurring with higher fre-quency in infant than non-infant B-ALL.1High-throughputsequencing identified these as NUT midline carcinoma familymember 1 (NUTM1) (15q14) rearrangements (NUTM1-r).2–7NUTM1-r were originally identified as the driving lesion ofNUT midline carcinomas (NMC), an aggressive malignancywith poor prognosis.8NUTM1-rinfant B-ALL however isassociated with favourable prognosis,3,9in contrast to infantswithKMT2Arearrangements.10Multiple 50partners havebeen identified inNUTM1-r B-ALL includingBRD9,IKZF1,CUX1,AFF1,ZNF618,SLC12A6, and the cytogeneticallycrypticACIN1.6NUTM1-r increasesNUTM1expression,3–6upregulatesHOX1family genes5and downregulatesNOTCHand Hedgehog pathways.5Rare cases of infant B-ALL thatco-harbourKMT2A-r andNUTM1-r have been reported2,6and no cases of adultNUTM1-r B-ALL have been identified.Here we report two unusual, high-risk presentations, ofNUTM1-r B-ALL characterised by early relapse.