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https://hdl.handle.net/2440/111892
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Type: | Journal article |
Title: | Pre-B acute lymphoblastic leukaemia recurrent fusion, EP300-ZNF384, is associated with a distinct gene expression |
Author: | McClure, B. Heatley, S. Kok, C. Sadras, T. An, J. Hughes, T. Lock, R. Yeung, D. Sutton, R. White, D. |
Citation: | British Journal of Cancer, 2018; 118(7):1000-1004 |
Publisher: | Nature Publishing Group |
Issue Date: | 2018 |
ISSN: | 0007-0920 1532-1827 |
Statement of Responsibility: | 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 |
DOI: | 10.1038/s41416-018-0022-0 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1057746 http://purl.org/au-research/grants/nhmrc/1044884 |
Published version: | http://dx.doi.org/10.1038/s41416-018-0022-0 |
Appears in Collections: | Aurora harvest 3 Medicine publications |
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