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The genetic basis of early T-cell precursor acute lymphoblastic leukaemia

Author

Listed:
  • Jinghui Zhang

    (St Jude Children’s Research Hospital)

  • Li Ding

    (The Genome Institute at Washington University
    Washington University School of Medicine)

  • Linda Holmfeldt

    (St Jude Children’s Research Hospital)

  • Gang Wu

    (St Jude Children’s Research Hospital)

  • Sue L. Heatley

    (St Jude Children’s Research Hospital
    Present addresses: Human Immunology, Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, 5000 Australia (S.L.H.); Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 119077 Singapore (D.C., E.C.-S.); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA (M.K.); Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA (M.I.B.).)

  • Debbie Payne-Turner

    (St Jude Children’s Research Hospital)

  • John Easton

    (Pediatric Cancer Genome Project Laboratory, St Jude Children’s Research Hospital)

  • Xiang Chen

    (St Jude Children’s Research Hospital)

  • Jianmin Wang

    (St Jude Children’s Research Hospital)

  • Michael Rusch

    (St Jude Children’s Research Hospital)

  • Charles Lu

    (The Genome Institute at Washington University)

  • Shann-Ching Chen

    (St Jude Children’s Research Hospital)

  • Lei Wei

    (St Jude Children’s Research Hospital)

  • J. Racquel Collins-Underwood

    (St Jude Children’s Research Hospital)

  • Jing Ma

    (St Jude Children’s Research Hospital)

  • Kathryn G. Roberts

    (St Jude Children’s Research Hospital)

  • Stanley B. Pounds

    (St Jude Children’s Research Hospital)

  • Anatoly Ulyanov

    (St Jude Children’s Research Hospital)

  • Jared Becksfort

    (St Jude Children’s Research Hospital)

  • Pankaj Gupta

    (St Jude Children’s Research Hospital)

  • Robert Huether

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

  • Richard W. Kriwacki

    (St Jude Children’s Research Hospital)

  • Matthew Parker

    (Pediatric Cancer Genome Project Laboratory, St Jude Children’s Research Hospital)

  • Daniel J. McGoldrick

    (St Jude Children’s Research Hospital)

  • David Zhao

    (St Jude Children’s Research Hospital)

  • Daniel Alford

    (St Jude Children’s Research Hospital)

  • Stephen Espy

    (St Jude Children’s Research Hospital)

  • Kiran Chand Bobba

    (St Jude Children’s Research Hospital)

  • Guangchun Song

    (St Jude Children’s Research Hospital)

  • Deqing Pei

    (St Jude Children’s Research Hospital)

  • Cheng Cheng

    (St Jude Children’s Research Hospital)

  • Stefan Roberts

    (Pediatric Cancer Genome Project Laboratory, St Jude Children’s Research Hospital)

  • Michael I. Barbato

    (Pediatric Cancer Genome Project Laboratory, St Jude Children’s Research Hospital
    Present addresses: Human Immunology, Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, 5000 Australia (S.L.H.); Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 119077 Singapore (D.C., E.C.-S.); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA (M.K.); Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA (M.I.B.).)

  • Dario Campana

    (St Jude Children’s Research Hospital
    Present addresses: Human Immunology, Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, 5000 Australia (S.L.H.); Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 119077 Singapore (D.C., E.C.-S.); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA (M.K.); Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA (M.I.B.).)

  • Elaine Coustan-Smith

    (St Jude Children’s Research Hospital
    Present addresses: Human Immunology, Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, 5000 Australia (S.L.H.); Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 119077 Singapore (D.C., E.C.-S.); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA (M.K.); Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA (M.I.B.).)

  • Sheila A. Shurtleff

    (St Jude Children’s Research Hospital)

  • Susana C. Raimondi

    (St Jude Children’s Research Hospital)

  • Maria Kleppe

    (Center for Human Genetics, VIB, K.U.Leuven, 3000 Leuven, Belgium
    Present addresses: Human Immunology, Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, 5000 Australia (S.L.H.); Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 119077 Singapore (D.C., E.C.-S.); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA (M.K.); Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA (M.I.B.).)

  • Jan Cools

    (Center for Human Genetics, VIB, K.U.Leuven, 3000 Leuven, Belgium)

  • Kristin A. Shimano

    (University of California School of Medicine)

  • Michelle L. Hermiston

    (University of California School of Medicine)

  • Sergei Doulatov

    (Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2M9, Canada
    University of Toronto, Toronto, Ontario M5S 1A8, Canada)

  • Kolja Eppert

    (Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2M9, Canada
    University of Toronto, Toronto, Ontario M5S 1A8, Canada)

  • Elisa Laurenti

    (Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2M9, Canada
    University of Toronto, Toronto, Ontario M5S 1A8, Canada)

  • Faiyaz Notta

    (Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2M9, Canada
    University of Toronto, Toronto, Ontario M5S 1A8, Canada)

  • John E. Dick

    (Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2M9, Canada
    University of Toronto, Toronto, Ontario M5S 1A8, Canada)

  • Giuseppe Basso

    (Onco-Hematology Laboratory, University of Padua)

  • Stephen P. Hunger

    (Section of Pediatric Hematology/Oncology/Bone Marrow Transplantation and Center for Cancer and Blood Disorders, University of Colorado Denver School of Medicine, Children’s Hospital Colorado)

  • Mignon L. Loh

    (University of California School of Medicine)

  • Meenakshi Devidas

    (University of Florida College of Medicine)

  • Brent Wood

    (Seattle Children’s Hospital)

  • Stuart Winter

    (University of New Mexico)

  • Kimberley P. Dunsmore

    (Pediatric Hematology Oncology, University of Virginia)

  • Robert S. Fulton

    (The Genome Institute at Washington University
    Washington University School of Medicine)

  • Lucinda L. Fulton

    (The Genome Institute at Washington University
    Washington University School of Medicine)

  • Xin Hong

    (The Genome Institute at Washington University)

  • Christopher C. Harris

    (The Genome Institute at Washington University)

  • David J. Dooling

    (The Genome Institute at Washington University
    Washington University School of Medicine)

  • Kerri Ochoa

    (The Genome Institute at Washington University)

  • Kimberly J. Johnson

    (The Genome Institute at Washington University)

  • John C. Obenauer

    (St Jude Children’s Research Hospital)

  • William E. Evans

    (St Jude Children’s Research Hospital)

  • Ching-Hon Pui

    (St Jude Children’s Research Hospital)

  • Clayton W. Naeve

    (St Jude Children’s Research Hospital)

  • Timothy J. Ley

    (The Genome Institute at Washington University
    Washington University
    Siteman Cancer Center, Washington University)

  • Elaine R. Mardis

    (The Genome Institute at Washington University
    Washington University School of Medicine
    Siteman Cancer Center, Washington University)

  • Richard K. Wilson

    (The Genome Institute at Washington University
    Washington University School of Medicine
    Siteman Cancer Center, Washington University)

  • James R. Downing

    (St Jude Children’s Research Hospital)

  • Charles G. Mullighan

    (St Jude Children’s Research Hospital)

Abstract

Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 and EP300) and histone-modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of recurrent mutation including DNM2, ECT2L and RELN. The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haematopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL.

Suggested Citation

  • Jinghui Zhang & Li Ding & Linda Holmfeldt & Gang Wu & Sue L. Heatley & Debbie Payne-Turner & John Easton & Xiang Chen & Jianmin Wang & Michael Rusch & Charles Lu & Shann-Ching Chen & Lei Wei & J. Racq, 2012. "The genetic basis of early T-cell precursor acute lymphoblastic leukaemia," Nature, Nature, vol. 481(7380), pages 157-163, January.
    • Handle: RePEc:nat:nature:v:481:y:2012:i:7380:d:10.1038_nature10725
    DOI: 10.1038/nature10725
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    Cited by:

    1. Roger Mulet-Lazaro & Stanley Herk & Margit Nuetzel & Aniko Sijs-Szabo & Noelia Díaz & Katherine Kelly & Claudia Erpelinck-Verschueren & Lucia Schwarzfischer-Pfeilschifter & Hanna Stanewsky & Ute Acker, 2024. "Epigenetic alterations affecting hematopoietic regulatory networks as drivers of mixed myeloid/lymphoid leukemia," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

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