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    DNA Methylation of the ABO Promoter Underlies Loss of ABO Allelic Expression in a Significant Proportion of Leukemic Patients

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    Author
    Bianco-Miotto, T; Hussey, DJ; Day, TK; O'Keefe, DS; Dobrovic, A
    Date
    2009-03-10
    Source Title
    PLoS One
    Publisher
    PUBLIC LIBRARY SCIENCE
    University of Melbourne Author/s
    Dobrovic, Alexander
    Affiliation
    Surgery (Austin & Northern Health)
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Bianco-Miotto, T., Hussey, D. J., Day, T. K., O'Keefe, D. S. & Dobrovic, A. (2009). DNA Methylation of the ABO Promoter Underlies Loss of ABO Allelic Expression in a Significant Proportion of Leukemic Patients. PLOS ONE, 4 (3), https://doi.org/10.1371/journal.pone.0004788.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/257290
    DOI
    10.1371/journal.pone.0004788
    Abstract
    BACKGROUND: Loss of A, B and H antigens from the red blood cells of patients with myeloid malignancies is a frequent occurrence. Previously, we have reported alterations in ABH antigens on the red blood cells of 55% of patients with myeloid malignancies. METHODOLOGY/PRINCIPAL FINDINGS: To determine the underlying molecular mechanisms of this loss, we assessed ABO allelic expression in 21 patients with ABH antigen loss previously identified by flow cytometric analysis as well as an additional 7 patients detected with ABH antigen changes by serology. When assessing ABO mRNA allelic expression, 6/12 (50%) patients with ABH antigen loss detected by flow cytometry and 5/7 (71%) of the patients with ABH antigen loss detected by serology had a corresponding ABO mRNA allelic loss of expression. We examined the ABO locus for copy number and DNA methylation alterations in 21 patients, 11 with loss of expression of one or both ABO alleles, and 10 patients with no detectable allelic loss of ABO mRNA expression. No loss of heterozygosity (LOH) at the ABO locus was observed in these patients. However in 8/11 (73%) patients with loss of ABO allelic expression, the ABO promoter was methylated compared with 2/10 (20%) of patients with no ABO allelic expression loss (P = 0.03). CONCLUSIONS/SIGNIFICANCE: We have found that loss of ABH antigens in patients with hematological malignancies is associated with a corresponding loss of ABO allelic expression in a significant proportion of patients. Loss of ABO allelic expression was strongly associated with DNA methylation of the ABO promoter.

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