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Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia

Gu, Z; Churchman, M; Roberts, K; Li, Y; Liu, Y; Harvey, RC; McCastlain, K; ... Mullighan, CG; + view all (2016) Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia. Nature Communications , 7 , Article 13331. 10.1038/ncomms13331. Green open access

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Abstract

Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitor treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukaemia, for which new therapeutic approaches should be considered.

Type: Article
Title: Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/ncomms13331
Publisher version: http://doi.org/10.1038/ncomms13331
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, FORKHEAD BOX J2, GENE-EXPRESSION, BREAST-CANCER, PROTEINS, RISK, IDENTIFICATION, TRANSFORMATION, MEF2D/DAZAP1, MIGRATION, PROGNOSIS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/1529031
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