title: Transglutaminase 2 expression in acute myeloid leukemia: association with adhesion molecule expression and leukemic blast motility.
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.
authors.affiliation: Stem Cell and Leukaemia Proteomics Laboratory, Manchester Academic Health Science Centre, Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Pierce
authors.affiliation: Stem Cell and Leukaemia Proteomics Laboratory, Manchester Academic Health Science Centre, Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Whetton
authors.affiliation: Stem Cell and Leukaemia Proteomics Laboratory, Manchester Academic Health Science Centre, Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK.
authors.forename: Stefan
authors.initials: S
authors.lastname: Meyer
authors.affiliation: Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi-Kashani
authors.affiliation: Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.affiliation: Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Coombes
authors.affiliation: Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Nianxiang
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Kornblau
mesh_terms: D000704:Analysis of Variance; D001854:Bone Marrow Cells / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D019204:GTP-Binding Proteins / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D007962:Leukocytes / Q000473:pathology; D009857:Oncogenes; D040081:Protein Array Analysis; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D060066:Protein Interaction Maps; D011503:Transglutaminases / Q000096:biosynthesis* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D015815:Cell Adhesion Molecules; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: Acute myeloid leukemia; Biomedicine; Reverse phase protein array; Transglutaminase2