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Blood, 15 February 2008, Vol. 111, No. 4, pp. 2382-2384. Prepublished online as a Blood First Edition Paper on November 30, 2007; DOI 10.1182/blood-2007-07-103960. This Article Full Text (PDF) All Versions of this Article: blood-2007-07-103960v1 111/4/2382    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Oki, Y. Articles by Issa, J.-P. J. Search for Related Content PubMed PubMed Citation Articles by Oki, Y. Articles by Issa, J.-P. J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 31, 2007 Accepted November 18, 2007 Induction of hypomethylation and molecular response after decitabine therapy in patients with chronic myelomonocytic leukemia Yasuhiro Oki, Jaroslav Jelinek, Lanlan Shen, Hagop M Kantarjian, and Jean-Pierre J. Issa* Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX, United States * Corresponding author; email: jpissa{at}mdanderson.org. Decitabine's mechanism of action in chronic myelomonocytic leukemia (CMML) remains incompletely understood. We studied the dynamics of neoplastic cell clearance during decitabine treatment (100 mg/m2/course every 4 weeks) using quantitative monitoring of mutant alleles by pyrosequencing. CMML patients were first screened for JAK2 and NPM1 mutations, and three patients with mutations were identified. Mutant allele percentages in mononuclear cell DNA were followed after treatment, along with methylation of LINE1 and ten other genes. The clearance of mutant alleles was modest after the first cycle, despite induction of hypomethylation. Delayed substantial clearance was observed after 2-4 cycles that correlated with clinical response. Two patients had complete disappearance of mutant alleles and sustained clinical remissions. In another patient, mutant allele was detectable at clinical remission, which lasted for 8 months. Our data suggest a predominantly non-cytotoxic mechanism of action for decitabine, leading to altered biology of the neoplastic clone and/or normal cells. This trial was registered at www.ClinicalTrials.gov as #NCT00067808. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. E. Fandy, J. G. Herman, P. Kerns, A. Jiemjit, E. A. Sugar, S.-H. Choi, A. S. Yang, T. Aucott, T. Dauses, R. Odchimar-Reissig, et al. Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies Blood, September 24, 2009; 114(13): 2764 - 2773. [Abstract] [Full Text] [PDF] M. Nojima, R. Maruyama, H. Yasui, H. Suzuki, Y. Maruyama, I. Tarasawa, Y. Sasaki, H. Asaoku, H. Sakai, T. Hayashi, et al. Genomic Screening for Genes Silenced by DNA Methylation Revealed an Association between RASD1 Inactivation and Dexamethasone Resistance in Multiple Myeloma Clin. Cancer Res., July 1, 2009; 15(13): 4356 - 4364. [Abstract] [Full Text] [PDF] J.-P. J. Issa and H. M. Kantarjian Targeting DNA Methylation Clin. Cancer Res., June 15, 2009; 15(12): 3938 - 3946. [Abstract] [Full Text] [PDF]

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