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Pre-B acute lymphoblastic leukaemia recurrent fusion, EP300-ZNF384, is associated with a distinct gene expression.
Br J Cancer 2018; 118(7):1000-1004BJ

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.

Authors+Show Affiliations

Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, 5000, Australia. School of Medicine, University of Adelaide, Adelaide, SA, 5000, Australia.Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, 5000, Australia. School of Medicine, University of Adelaide, Adelaide, SA, 5000, Australia.Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, 5000, Australia. School of Medicine, University of Adelaide, Adelaide, SA, 5000, Australia.Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, 5000, Australia. School of Medicine, University of Adelaide, Adelaide, SA, 5000, Australia.Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, 5000, Australia.Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, 5000, Australia. School of Medicine, University of Adelaide, Adelaide, SA, 5000, Australia. Haematology Department, SA Pathology, Adelaide, SA, 5000, Australia.Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, 2000, Australia. School of Women's and Children's Health, University of New South Wales, Sydney, NSW, 2000, Australia.Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, 5000, Australia. School of Medicine, University of Adelaide, Adelaide, SA, 5000, Australia. Haematology Department, SA Pathology, Adelaide, SA, 5000, Australia.Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, 2000, Australia. School of Women's and Children's Health, University of New South Wales, Sydney, NSW, 2000, Australia. Australian Genomics Health Alliance (AGHA), Murdoch Children's Research Institute, Parkville, VIC, 3052, Australia.Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, 5000, Australia. deborah.white@sahmri.com. School of Medicine, University of Adelaide, Adelaide, SA, 5000, Australia. deborah.white@sahmri.com. Australian Genomics Health Alliance (AGHA), Murdoch Children's Research Institute, Parkville, VIC, 3052, Australia. deborah.white@sahmri.com. School of Paediatrics, University of Adelaide, Adelaide, SA, 5000, Australia. deborah.white@sahmri.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29531323

Citation

McClure, Barbara J., et al. "Pre-B Acute Lymphoblastic Leukaemia Recurrent Fusion, EP300-ZNF384, Is Associated With a Distinct Gene Expression." British Journal of Cancer, vol. 118, no. 7, 2018, pp. 1000-1004.
McClure BJ, Heatley SL, Kok CH, et al. Pre-B acute lymphoblastic leukaemia recurrent fusion, EP300-ZNF384, is associated with a distinct gene expression. Br J Cancer. 2018;118(7):1000-1004.
McClure, B. J., Heatley, S. L., Kok, C. H., Sadras, T., An, J., Hughes, T. P., ... White, D. L. (2018). Pre-B acute lymphoblastic leukaemia recurrent fusion, EP300-ZNF384, is associated with a distinct gene expression. British Journal of Cancer, 118(7), pp. 1000-1004. doi:10.1038/s41416-018-0022-0.
McClure BJ, et al. Pre-B Acute Lymphoblastic Leukaemia Recurrent Fusion, EP300-ZNF384, Is Associated With a Distinct Gene Expression. Br J Cancer. 2018;118(7):1000-1004. PubMed PMID: 29531323.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pre-B acute lymphoblastic leukaemia recurrent fusion, EP300-ZNF384, is associated with a distinct gene expression. AU - McClure,Barbara J, AU - Heatley,Susan L, AU - Kok,Chung H, AU - Sadras,Teresa, AU - An,Jiyuan, AU - Hughes,Timothy P, AU - Lock,Richard B, AU - Yeung,David, AU - Sutton,Rosemary, AU - White,Deborah L, Y1 - 2018/03/13/ PY - 2017/09/07/received PY - 2018/01/18/accepted PY - 2017/12/22/revised PY - 2018/3/14/pubmed PY - 2019/6/4/medline PY - 2018/3/14/entrez SP - 1000 EP - 1004 JF - British journal of cancer JO - Br. J. Cancer VL - 118 IS - 7 N2 - 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. SN - 1532-1827 UR - https://www.unboundmedicine.com/medline/citation/29531323/Pre_B_acute_lymphoblastic_leukaemia_recurrent_fusion_EP300_ZNF384_is_associated_with_a_distinct_gene_expression_ L2 - http://dx.doi.org/10.1038/s41416-018-0022-0 DB - PRIME DP - Unbound Medicine ER -