Pre-B Acute Lymphoblastic Leukaemia Recurrent Fusion, EP300-ZNF384, is Associated with a Distinct Gene Expression

Overview

Journal Br J Cancer

Specialty Oncology

Date 2018 Mar 14

PMID 29531323

Citations 22

Authors

Barbara J McClure

Susan L Heatley

Chung H Kok

Teresa Sadras

Jiyuan An

Timothy P Hughes

Richard B Lock

David Yeung

Rosemary Sutton

Deborah L White

Affiliations

Soon will be listed here.

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.

Citing Articles

RanBALL: An Ensemble Random Projection Model for Identifying Subtypes of B-Cell Acute Lymphoblastic Leukemia.

Li L, Xiao H, Wu X, Tang Z, Khoury J, Wang J bioRxiv. 2024; .

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The Molecular and Biological Function of MEF2D in Leukemia.

Zhang P, Lu R Adv Exp Med Biol. 2024; 1459:379-403.

PMID: 39017853 DOI: 10.1007/978-3-031-62731-6_17.

EP300-ZNF384 transactivates IL3RA to promote the progression of B-cell acute lymphoblastic leukemia.

Hou Z, Ren Y, Zhang X, Huang D, Yan F, Sun W Cell Commun Signal. 2024; 22(1):211.

PMID: 38566191 PMC: 10986138. DOI: 10.1186/s12964-024-01596-9.

The Gene Expression Classifier ALLCatchR Identifies B-cell Precursor ALL Subtypes and Underlying Developmental Trajectories Across Age.

Beder T, Hansen B, Hartmann A, Zimmermann J, Amelunxen E, Wolgast N Hemasphere. 2023; 7(9):e939.

PMID: 37645423 PMC: 10461941. DOI: 10.1097/HS9.0000000000000939.

Zhu L, Bai W, Cheng Q, Fang J Cancer Control. 2023; 30:10732748231182787.

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