Acute B lymphoblastic leukaemia-propagating cells are present at high frequency in diverse lymphoblast populations

Authors

  • Klaus Rehe,

    1. Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK
    2. Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
    3. Present address: KUNO Children's Hospital, Pediatric Hematology, Oncology and Stem Cell Transplantation, University Medical Center Regensburg, Regensburg, Germany
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  • Kerrie Wilson,

    1. Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK
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  • Simon Bomken,

    1. Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK
    2. Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
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  • Daniel Williamson,

    1. Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK
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  • Julie Irving,

    1. Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK
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  • Monique L. den Boer,

    1. Department of Pediatric Oncology and Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
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  • Martin Stanulla,

    1. Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
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  • Martin Schrappe,

    1. Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
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  • Andrew G. Hall,

    1. Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK
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  • Olaf Heidenreich,

    1. Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK
    2. North of England Stem Cell Institute, Newcastle University, Newcastle upon Tyne, UK
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  • Josef Vormoor

    Corresponding author
    1. Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK
    2. Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
    3. North of England Stem Cell Institute, Newcastle University, Newcastle upon Tyne, UK
    • Tel: +44 191 28 21357; Fax: +44 191 28 24724

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Abstract

Leukaemia-propagating cells are more frequent in high-risk acute B lymphoblastic leukaemia than in many malignancies that follow a hierarchical cancer stem cell model. It is unclear whether this characteristic can be more universally applied to patients from non-‘high-risk’ sub-groups and across a broad range of cellular immunophenotypes. Here, we demonstrate in a wide range of primary patient samples and patient samples previously passaged through mice that leukaemia-propagating cells are found in all populations defined by high or low expression of the lymphoid differentiation markers CD10, CD20 or CD34. The frequency of leukaemia-propagating cells and their engraftment kinetics do not differ between these populations. Transcriptomic analysis of CD34high and CD34low blasts establishes their difference and their similarity to comparable normal progenitors at different stages of B-cell development. However, consistent with the functional similarity of these populations, expression signatures characteristic of leukaemia propagating cells in acute myeloid leukaemia fail to distinguish between the different populations. Together, these findings suggest that there is no stem cell hierarchy in acute B lymphoblastic leukaemia.

→See accompanying article http://dx.doi.org/10.1002/emmm.201202207

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