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Blood, 15 October 2009, Vol. 114, No. 16, pp. 3448-3458. Prepublished online as a Blood First Edition Paper on August 3, 2009; DOI 10.1182/blood-2009-01-200519. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2009-01-200519v1 114/16/3448    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 Google Scholar Articles by Figueroa, M. E. Articles by Melnick, A. PubMed PubMed Citation Articles by Figueroa, M. E. Articles by Melnick, A. Related Collections Myeloid Neoplasia Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  MYELOID NEOPLASIA MDS and secondary AML display unique patterns and abundance of aberrant DNA methylation Maria E. Figueroa1, Lucy Skrabanek2, Yushan Li1, Anchalee Jiemjit3, Tamer E. Fandy3, Elisabeth Paietta4, Hugo Fernandez5, Martin S. Tallman6, John M. Greally7, Hetty Carraway3, Jonathan D. Licht6, Steven D. Gore3, and Ari Melnick1 1 Department of Medicine (Hematology Oncology Division), and 2 HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine and Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY; 3 Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD; 4 Division of Hematology and Oncology, Department of Medicine, Montefiore Medical Center, Our Lady of Mercy Campus, Bronx, NY; 5 Department of Blood and Marrow Transplantation, Moffit Cancer Center and Research Institute, Tampa, FL; 6 Division of Hematology and Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL; and 7 Department of Genetics, Albert Einstein College of Medicine, Bronx, NY Increasing evidence shows aberrant hypermethylation of genes occurring in and potentially contributing to pathogenesis of myeloid malignancies. Several of these diseases, such as myelodysplastic syndromes (MDSs), are responsive to DNA methyltransferase inhibitors. To determine the extent of promoter hypermethylation in such tumors, we compared the distribution of DNA methylation of 14 000 promoters in MDS and secondary acute myeloid leukemia (AML) patients enrolled in a phase 1 trial of 5-azacytidine and the histone deacetylase inhibitor entinostat against de novo AML patients and normal CD34+ bone marrow cells. The MDS and secondary AML patients displayed more extensive aberrant DNA methylation involving thousands of genes than did the normal CD34+ bone marrow cells or de novo AML blasts. Aberrant methylation in MDS and secondary AML tended to affect particular chromosomal regions, occurred more frequently in Alu-poor genes, and included prominent involvement of genes involved in the WNT and MAPK signaling pathways. DNA methylation was also measured at days 15 and 29 after the first treatment cycle. DNA methylation was reversed at day 15 in a uniform manner throughout the genome, and this effect persisted through day 29, even without continuous administration of the study drugs. This trial was registered at www.clinicaltrials.gov as J0443. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Through the looking glass Joshi J. Alumkal Blood 2009 114: 3363-3364. [Full Text] [PDF] This article has been cited by other articles: J. J. Alumkal Through the looking glass Blood, October 15, 2009; 114(16): 3363 - 3364. [Full Text] [PDF]

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