Pre-B acute lymphoblastic leukaemia recurrent fusion, EP300-ZNF384, is associated with a distinct gene expression

Barbara McClure, Susan Heatley, Chung Kok, Teresa Sadras, Jiyuan An, Timothy Hughes, Richard B. Lock, David Yeung, Rosemary Sutton, Deborah White

Research output: Contribution to journalArticle

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.

LanguageEnglish
Pages1000-1004
Number of pages5
JournalBritish Journal of Cancer
Volume118
Issue number7
DOIs
Publication statusPublished - 1 Apr 2018

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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title = "Pre-B acute lymphoblastic leukaemia recurrent fusion, EP300-ZNF384, is associated with a distinct gene expression",
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.",
author = "Barbara McClure and Susan Heatley and Chung Kok and Teresa Sadras and Jiyuan An and Timothy Hughes and Lock, {Richard B.} and David Yeung and Rosemary Sutton and Deborah White",
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Pre-B acute lymphoblastic leukaemia recurrent fusion, EP300-ZNF384, is associated with a distinct gene expression. / McClure, Barbara; Heatley, Susan; Kok, Chung; Sadras, Teresa; An, Jiyuan; Hughes, Timothy; Lock, Richard B.; Yeung, David; Sutton, Rosemary; White, Deborah.

In: British Journal of Cancer, Vol. 118, No. 7, 01.04.2018, p. 1000-1004.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pre-B acute lymphoblastic leukaemia recurrent fusion, EP300-ZNF384, is associated with a distinct gene expression

AU - McClure, Barbara

AU - Heatley, Susan

AU - Kok, Chung

AU - Sadras, Teresa

AU - An, Jiyuan

AU - Hughes, Timothy

AU - Lock, Richard B.

AU - Yeung, David

AU - Sutton, Rosemary

AU - White, Deborah

PY - 2018/4/1

Y1 - 2018/4/1

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.

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