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Blood, 26 February 2009, Vol. 113, No. 9, pp. 1892-1898. Prepublished online as a Blood First Edition Paper on December 23, 2008; DOI 10.1182/blood-2008-02-141002. This Article Full Text (PDF) All Versions of this Article: blood-2008-02-141002v1 113/9/1892    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yang, H. Articles by Garcia-Manero, G. Search for Related Content PubMed PubMed Citation Articles by Yang, H. Articles by Garcia-Manero, G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 27, 2008 Accepted November 24, 2008 Residual DNA methylation at remission is prognostic in adult Philadelphia chromosome negative acute lymphocytic leukemia Hui Yang, Tapan Kadia, Lianchun Xiao, Carlos E. Bueso-Ramos, Koyu Hoshino, Deborah Ann Thomas, Susan O'Brien, Elias Jabbour, Sherry Pierce, Gary L. Rosner, Hagop M Kantarjian, and Guillermo Garcia-Manero* Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, United States Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, United States Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, United States * Corresponding author; email: ggarciam{at}mdanderson.org. Pretreatment aberrant DNA methylation patterns are stable at time of relapse in acute lymphocytic leukemia (ALL). We hypothesized that the detection of residual methylation alterations at the time of morphological remission may predict for worse prognosis. We developed a real-time bisulfite PCR assay and analyzed the methylation levels of p73, p15 and p57KIP2 at the time of initial remission in 199 patients with Philadelphia chromosome and MLL negative ALL. Residual p73 methylation was detected in 18 (9.5%) patients, p15 in 33 (17.4%), and p57KIP2 in 7 (3.7%); 140 (74%) patients had methylation of 0 genes and 48 (25%) of 1 gene. In 123 (65%) patients, matched pretreatment samples were also studied and compared to remission ones: in 82 of those with initial aberrant methylation of at least one gene, 59 (72%) had no detectable methylation at remission, and 23 (28%) had detectable residual methylation. By multivariate analysis, presence of residual p73 methylation was associated with a significant shorter duration of first complete remission (HR 2.68, p=0.003), and overall survival (HR 2.69, p=0.002). In conclusion, detection of specific epigenetic alterations may allow the identification of patients with ALL with standard risk disease but with a poor prognosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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