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Transglutaminase 2 expression in acute myeloid leukemia: Association with adhesion molecule expression and leukemic blast motility

Authors

  • Andrew Pierce,

    1. Stem Cell and Leukaemia Proteomics Laboratory, Manchester Academic Health Science Centre, Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK
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    • These authors contributed equally to this work.

  • Anthony D. Whetton,

    Corresponding author
    • Stem Cell and Leukaemia Proteomics Laboratory, Manchester Academic Health Science Centre, Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK
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    • These authors contributed equally to this work.

  • Stefan Meyer,

    1. Stem Cell and Leukaemia Proteomics Laboratory, Manchester Academic Health Science Centre, Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK
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  • Farhad Ravandi-Kashani,

    1. Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
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  • Gautam Borthakur,

    1. Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
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  • Kevin R. Coombes,

    1. Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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  • Nianxiang Zhang,

    1. Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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  • Steven Kornblau

    Corresponding author
    • Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
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  • Colour Online: See the article online to view Fig. 3 in colour.

Correspondence: Professor Anthony D. Whetton, Stem Cell and Leukaemia Proteomics Laboratory, Manchester Academic Health Science Centre, Wolfson Molecular Imaging Centre, The University of Manchester, 27 Palatine Road, Withington, Manchester M20 3LJ, UK

E-mail: Tony.whetton@manchester.ac.uk

Additional corresponding author: Dr. S. Kornblau,

E-mail: skornblau@mdanderson.org

Abstract

Acute myeloid leukemia (AML) is a heterogenous disease with differential oncogene association, outcome and treatment regimens. Treatment strategies for AML have improved outcome but despite increased molecular biological information AML is still associated with poor prognosis. Proteomic analysis on the effects of a range of leukemogenic oncogenes showed that the protein transglutaminase 2 (TG2) is expressed at greater levels as a consequence of oncogenic transformation. Further analysis of this observation was performed with 511 AML samples using reverse phase proteomic arrays, demonstrating that TG2 expression was higher at relapse than diagnosis in many cases. In addition elevated TG2 expression correlated with increased expression of numerous adhesion proteins and many apoptosis regulating proteins, two processes related to leukemogenesis. TG2 has previously been linked to drug resistance in cancer and given the negative correlation between TG2 levels and peripheral blasts observed increased TG2 levels may lead to the protection of the leukemic stem cell due to increased adhesion/reduced motility. TG2 may therefore form part of a network of proteins that define poor outcome in AML patients and potentially offer a target to sensitize AML stem cells to drug treatment.

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