Please use this identifier to cite or link to this item:
Scopus Web of Science® Altmetric
Type: Journal article
Title: Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia
Author: Gu, Z.
Churchman, M.
Roberts, K.
Li, Y.
Liu, Y.
Harvey, R.
McCastlain, K.
Reshmi, S.
Payne-Turner, D.
Iacobucci, I.
Shao, Y.
Chen, I.
Valentine, M.
Pei, D.
Mungall, K.
Mungall, A.
Ma, Y.
Moore, R.
Marra, M.
Stonerock, E.
et al.
Citation: Nature Communications, 2016; 7:13331-1-13331-10
Publisher: Nature Publishing Group
Issue Date: 2016
ISSN: 2041-1723
Statement of
Zhaohui Gu, ... Charles G. Mullighan, ... et al.
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 MEF2DBCL9. 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.
Keywords: NIH 3T3 Cells; Animals; Humans; Mice; Luciferases; Oncogene Proteins, Fusion; Treatment Outcome; Sequence Analysis, RNA; Genomics; Gene Expression Regulation, Leukemic; Gene Rearrangement; Base Sequence; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Histone Deacetylase Inhibitors; Transcriptome; MEF2 Transcription Factors
Rights: © The Author(s) 2016, 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
RMID: 0030061186
DOI: 10.1038/ncomms13331
Appears in Collections:Medicine publications

Files in This Item:
File Description SizeFormat 
hdl_104503.pdfPublished version1.19 MBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.