Recurrent DUX4 fusions in B cell acute lymphoblastic leukemia of adolescents and young adults
Menée au Japon à partir d'échantillons prélevés sur 73 patients adolescents et jeunes adultes atteints d'une leucémie lymphoblastique aiguë Ph- (âge compris entre 15 et 39 ans), cette étude identifie la présence fréquente de réarrangements chromosomiques impliquant le gène DUX4 dans les leucémies de type B
The oncogenic mechanisms underlying acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA; 15–39 years old) remain largely elusive. Here we have searched for new oncogenes in AYA-ALL by performing RNA-seq analysis of Philadelphia chromosome (Ph)-negative AYA-ALL specimens (n = 73) with the use of a next-generation sequencer. Interestingly, insertion of D4Z4 repeats containing the DUX4 gene into the IGH locus was frequently identified in B cell AYA-ALL, leading to a high level of expression of DUX4 protein with an aberrant C terminus. A transplantation assay in mice demonstrated that expression of DUX4-IGH in pro-B cells was capable of generating B cell leukemia in vivo. DUX4 fusions were preferentially detected in the AYA generation. Our data thus show that DUX4 can become an oncogenic driver as a result of somatic chromosomal rearrangements and that AYA-ALL may be a clinical entity distinct from ALL at other ages.