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|Title:||Pre-B acute lymphoblastic leukaemia recurrent fusion, EP300-ZNF384, is associated with a distinct gene expression|
|Citation:||British Journal of Cancer, 2018; 118(7):1000-1004|
|Publisher:||Nature Publishing Group|
|Barbara J. McClure, Susan L. Heatley, Chung H Kok, Teresa Sadras, Jiyuan An, Timothy P. Hughes, Richard B. Lock, David Yeung, Rosemary Sutton and Deborah L White|
|Abstract:||BACKGROUND: Zinc-finger protein 384 (ZNF384) fusions are an emerging subtype of precursor B-cell acute lymphoblastic leukaemia (pre-B-ALL) and here we further characterised their prevalence, survival outcomes and transcriptome. METHODS: Bone marrow mononuclear cells from 274 BCR-ABL1-negative pre-B-ALL patients were immunophenotyped and transcriptome molecularly characterised. Transcriptomic data was analysed by principal component analysis and gene-set enrichment analysis to identify gene and pathway expression changes. RESULTS: We exclusively detect E1A-associated protein p300 (EP300)-ZNF384 in 5.7% of BCR-ABL1-negative adolescent/young adult (AYA)/adult pre-B-ALL patients. EP300-ZNF384 patients do not appear to be a high-risk subgroup. Transcriptomic analysis revealed that EP300-ZNF384 samples have a distinct gene expression profile that results in the up-regulation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) and cell adhesion pathways and down-regulation of cell cycle and DNA repair pathways. CONCLUSIONS: Importantly, this report contributes to a better overview of the incidence of EP300-ZNF384 patients and show that they have a distinct gene signature with concurrent up-regulation of JAK-STAT pathway, reduced expression of B-cell regulators and reduced DNA repair capacity.|
|Keywords:||Humans; Recurrence; Trans-Activators; Oncogene Proteins, Fusion; Survival Analysis; Gene Expression Profiling; Signal Transduction; Gene Expression Regulation, Leukemic; Gene Frequency; Genes, abl; Adolescent; Adult; Child; Female; Male; STAT Transcription Factors; E1A-Associated p300 Protein; Janus Kinases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Young Adult; Transcriptome|
|Rights:||© Cancer Research UK 2018|
|Appears in Collections:||Medicine publications|
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