Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/60344
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Type: Journal article
Title: DNA methylation of the ABO promoter underlies loss of ABO allelic expression in a significant proportion of leukemic patients
Author: Bianco-Miotto, T.
Hussey, D.
Day, T.
O'Keefe, D.
Dobrovic, A.
Citation: PLoS One, 2009; 4(3):1-8
Publisher: Public Library of Science
Issue Date: 2009
ISSN: 1932-6203
1932-6203
Statement of
Responsibility: 
Tina Bianco-Miotto, Damian J. Hussey, Tanya K. Day, Denise S. O'Keefe and Alexander Dobrovic
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.
Keywords: Humans; Leukemia; Myeloproliferative Disorders; RNA, Messenger; ABO Blood-Group System; Isoantigens; DNA Methylation; Gene Dosage; Loss of Heterozygosity; Promoter Regions, Genetic
Rights: Copyright: © 2009 Bianco-Miotto et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0020091255
DOI: 10.1371/journal.pone.0004788
Appears in Collections:Medicine publications

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