Abstract
ERG-related leukemia is a B cell precursor acute lymphoblastic leukemia (BCP ALL) subtype characterized by aberrant expression of DUX4 and ERG transcription factors, and highly recurrent ERG intragenic deletions. ERG-related patients have remarkably favorable outcome despite a high incidence of inauspicious IKZF1 aberrations.We describe clinical and genomic features of the ERG-related cases in an unselected cohort of B-other BCP ALL pediatric patients enrolled in the AIEOP ALL 2000 therapeutic protocol. We report a small noncoding RNA signature specific of ERG-related group, with up-regulation of miR-125b-2 cluster on chromosome 21 and several snoRNAs in the Prader-Willi locus at 15q11.2, including the orphan SNORD116 cluster.
Highlights
Childhood B cell precursor acute lymphoblastic leukemia (BCPALL) is an heterogeneous disease characterized by recurrent genetic aberrations and frequent mutations of genes involved in hematopoietic development, patients that lack common aberrations are defined “B-others” [1].ERG-related leukemia is a BCP ALL subtype firstly identified by Yeoh and colleagues in the beginning of the gene expression era as a group of B-others characterized by a unique gene expression profile [2]
We describe clinical and genomic features of the ERG-related cases in an unselected cohort of B-other BCP ALL pediatric patients enrolled in the AIEOP ALL 2000 therapeutic protocol
Event-free survival (EFS) and cumulative relapse incidence (CRI) analysis revealed no significant differences between B-others included and not included in the study (Supplementary Figure 1)
Summary
Childhood B cell precursor acute lymphoblastic leukemia (BCPALL) is an heterogeneous disease characterized by recurrent genetic aberrations and frequent mutations of genes involved in hematopoietic development, patients that lack common aberrations are defined “B-others” [1].ERG-related leukemia is a BCP ALL subtype firstly identified by Yeoh and colleagues in the beginning of the gene expression era as a group of B-others characterized by a unique gene expression profile [2]. Recent studies uncovered IGH-DUX4 rearrangements, and rare ERGDUX4 rearrangements, as universal feature and founder event in the ERG-related leukemia subtype [3,4,5,6]. In these DUX4 rearranged leukemias, the double-homeobox transcription factor DUX4 is in most cases placed under the control of the immunoglobulin heavy chain enhancer, is expressed at high level and activates transcription of many genes including a novel ERG (v-ets erythroblastosis virus E26 oncogene homolog) isoform called “ERGalt”. ERGrelated patients were associated to a favorable outcome [10] despite a marked incidence of IKZF1 aberrations, a known unfavorable prognostic marker in BCP ALL [8, 9]
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