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Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia

Author

Listed:
  • Zhaohui Gu

    (St Jude Children’s Research Hospital)

  • Michelle Churchman

    (St Jude Children’s Research Hospital)

  • Kathryn Roberts

    (St Jude Children’s Research Hospital)

  • Yongjin Li

    (St Jude Children’s Research Hospital)

  • Yu Liu

    (St Jude Children’s Research Hospital)

  • Richard C. Harvey

    (University of New Mexico Cancer Center)

  • Kelly McCastlain

    (St Jude Children’s Research Hospital)

  • Shalini C. Reshmi

    (The Research Institute, Nationwide Children’s Hospital)

  • Debbie Payne-Turner

    (St Jude Children’s Research Hospital)

  • Ilaria Iacobucci

    (St Jude Children’s Research Hospital)

  • Ying Shao

    (St Jude Children’s Research Hospital
    St Jude Children’s Research Hospital)

  • I-Ming Chen

    (University of New Mexico Cancer Center)

  • Marcus Valentine

    (Cytogenetic Shared Resource, St Jude Children’s Research Hospital)

  • Deqing Pei

    (St Jude Children’s Research Hospital)

  • Karen L. Mungall

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency)

  • Andrew J. Mungall

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency)

  • Yussanne Ma

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency)

  • Richard Moore

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency)

  • Marco Marra

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency)

  • Eileen Stonerock

    (Nationwide Children’s Hospital
    The Ohio State University College of Medicine
    The Ohio State University College of Medicine)

  • Julie M. Gastier-Foster

    (Nationwide Children’s Hospital
    The Ohio State University College of Medicine
    The Ohio State University College of Medicine)

  • Meenakshi Devidas

    (Colleges of Medicine and Public Health & Health Professions, University of Florida)

  • Yunfeng Dai

    (Colleges of Medicine and Public Health & Health Professions, University of Florida)

  • Brent Wood

    (University of Washington)

  • Michael Borowitz

    (Johns Hopkins Medical Institutions)

  • Eric E. Larsen

    (Maine Children’s Cancer Program)

  • Kelly Maloney

    (Pediatric Hematology/Oncology/BMT, University of Colorado School of Medicine and Children’s Hospital Colorado)

  • Leonard A. Mattano Jr

    (HARP Pharma Consulting)

  • Anne Angiolillo

    (Children's National Medical Center)

  • Wanda L. Salzer

    (US Army Medical Research and Materiel Command)

  • Michael J. Burke

    (Medical College of Wisconsin)

  • Francesca Gianni

    (Papa Giovanni XXIII Hospital)

  • Orietta Spinelli

    (Papa Giovanni XXIII Hospital)

  • Jerald P. Radich

    (Fred Hutchinson Cancer Research Center)

  • Mark D. Minden

    (Princess Margaret Cancer Centre, University Health Network)

  • Anthony V. Moorman

    (Leukemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University)

  • Bella Patel

    (Barts Cancer Institute)

  • Adele K. Fielding

    (UCL Cancer Institute)

  • Jacob M. Rowe

    (Hematology, Shaare Zedek Medical Center)

  • Selina M. Luger

    (Abramson Cancer Center, University of Pennsylvania)

  • Ravi Bhatia

    (The University of Alabama at Birmingham)

  • Ibrahim Aldoss

    (The University of Alabama at Birmingham)

  • Stephen J. Forman

    (Gehr Family Center for Leukemia Research, City of Hope)

  • Jessica Kohlschmidt

    (The Ohio State University Comprehensive Cancer Center
    Alliance for Clinical Trials in Oncology Statistics and Data Center, Mayo Clinic)

  • Krzysztof Mrózek

    (The Ohio State University Comprehensive Cancer Center)

  • Guido Marcucci

    (Gehr Family Center for Leukemia Research, City of Hope)

  • Clara D. Bloomfield

    (The Ohio State University Comprehensive Cancer Center)

  • Wendy Stock

    (University of Chicago Medical Center)

  • Steven Kornblau

    (The University of Texas MD Anderson Cancer Center)

  • Hagop M. Kantarjian

    (The University of Texas MD Anderson Cancer Center)

  • Marina Konopleva

    (The University of Texas MD Anderson Cancer Center)

  • Elisabeth Paietta

    (Cancer Center)

  • Cheryl L. Willman

    (University of New Mexico Cancer Center)

  • Mignon L. Loh

    (Benioff Children’s Hospital
    Helen Diller Family Comprehensive Cancer Center)

  • Stephen P. Hunger

    (Children’s Hospital of Philadelphia
    Perelman School of Medicine at the University of Pennsylvania)

  • Charles G. Mullighan

    (St Jude Children’s Research Hospital)

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.

Suggested Citation

  • Zhaohui Gu & Michelle Churchman & Kathryn Roberts & Yongjin Li & Yu Liu & Richard C. Harvey & Kelly McCastlain & Shalini C. Reshmi & Debbie Payne-Turner & Ilaria Iacobucci & Ying Shao & I-Ming Chen & , 2016. "Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia," Nature Communications, Nature, vol. 7(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13331
    DOI: 10.1038/ncomms13331
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    Cited by:

    1. Ting Liu & Jianan Rao & Wenting Hu & Bowen Cui & Jiaoyang Cai & Yuhan Liu & Huiying Sun & Xiaoxiao Chen & Yanjing Tang & Jing Chen & Xiang Wang & Han Wang & Wubin Qian & Binchen Mao & Sheng Guo & Rong, 2022. "Distinct genomic landscape of Chinese pediatric acute myeloid leukemia impacts clinical risk classification," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Isabelle Rose Leo & Luay Aswad & Matthias Stahl & Elena Kunold & Frederik Post & Tom Erkers & Nona Struyf & Georgios Mermelekas & Rubin Narayan Joshi & Eva Gracia-Villacampa & Päivi Östling & Olli P. , 2022. "Integrative multi-omics and drug response profiling of childhood acute lymphoblastic leukemia cell lines," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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