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Prepublished online as a Blood First Edition Paper on February 13, 2003; DOI 10.1182/blood-2002-08-2466. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-08-2466v1 101/10/4131    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Shen, L. Articles by Garcia-Manero, G. Search for Related Content PubMed PubMed Citation Articles by Shen, L. Articles by Garcia-Manero, G. Related Collections Neoplasia Cell Cycle Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 May 2003, Vol. 101, No. 10, pp. 4131-4136 NEOPLASIA Aberrant DNA methylation of p57KIP2 identifies a cell-cycle regulatory pathway with prognostic impact in adult acute lymphocytic leukemia LanLan Shen, Minoru Toyota, Yutaka Kondo, Toshiro Obata, Sophia Daniel, Sherry Pierce, Kohzoh Imai, Hagop M. Kantarjian, Jean-Pierre J. Issa, and Guillermo Garcia-Manero From the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX; and the First Department of Internal Medicine and the Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University, Sapporo, Japan. P57KIP2 is a cyclin-dependent kinase inhibitor silenced in a variety of human malignancies. DNA methylation of a region surrounding the transcription start site of p57KIP2 was found in acute lymphocytic leukemia (ALL)-derived cell lines. Methylation of this region correlated with gene silencing, and treatment of methylated/silenced cell lines with 5-aza-2'-deoxycytidine resulted in gene re-expression. P57KIP2 was methylated in 31 (50%) of 63 patients with newly diagnosed ALL, and in 11 (52%) of 21 patients with relapsed ALL. In 5 of them (25%), methylation was acquired at relapse. No association was observed between methylation of p57KIP2 alone and clinical-biologic characteristics studied, including overall survival (OS) or disease-free survival. Methylation of multiple genes in a cell-cycle regulatory pathway composed of p73, p15, and p57KIP2 occurred in 22% of Philadelphia chromosome (Ph)-negative patients. Ph-negative patients with methylation of 2 or 3 genes of this pathway had a significantly worse median OS compared with those with methylation of 0 or 1 gene (50 vs 467 weeks, respectively; P = .02). Our results indicate that p57KIP2 is frequently methylated in adult patients with ALL, and that inactivation of a pathway composed of p73, p15, and p57KIP2 predicts for poor prognosis in Ph-negative patients. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Yang, T. Kadia, L. Xiao, C. E. Bueso-Ramos, K. Hoshino, D. A. Thomas, S. O'Brien, E. Jabbour, S. Pierce, G. L. Rosner, et al. Residual DNA methylation at remission is prognostic in adult Philadelphia chromosome-negative acute lymphocytic leukemia Blood, February 26, 2009; 113(9): 1892 - 1898. [Abstract] [Full Text] [PDF] H. Kroeger, J. Jelinek, M. R. H. Estecio, R. He, K. Kondo, W. Chung, L. Zhang, L. 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