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Blood, 15 January 2004, Vol. 103, No. 2, pp. 698-700. Prepublished online as a Blood First Edition Paper on September 22, 2003; DOI 10.1182/blood-2003-07-2249. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-07-2249v1 103/2/698    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 Voso, M. T. Articles by Leone, G. Search for Related Content PubMed PubMed Citation Articles by Voso, M. T. Articles by Leone, G. Related Collections Neoplasia Apoptosis Oncogenes and Tumor Suppressors Signal Transduction Brief Reports Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Brief report Aberrant methylation of DAP-kinase in therapy-related acute myeloid leukemia and myelodysplastic syndromes Maria Teresa Voso, Alessandra Scardocci, Francesco Guidi, Gina Zini, Antonella Di Mario, Livio Pagano, Stefan Hohaus, and Giuseppe Leone From the Istituto di Ematologia, Università Cattolica S. Cuore, Rome, Italy. Death-associated protein kinase (DAP-kinase), a proapoptotic serine/threonine kinase, is a candidate tumor suppressor gene. We studied the methylation status of DAP-kinase of 194 bone marrow samples from 160 patients with acute myeloid leukemia (AML) and 34 with a myelodysplastic syndrome (MDS) at the time of initial diagnosis by polymerase chain reaction (PCR). Hypermethylation of DAP-kinase was present in 27.5% (44 of 160) of AML and in 47% (16 of 34) of MDS specimens and significantly correlated to loss of DAP-kinase expression (P = .008). It was significantly more frequent in AML secondary to therapy for other malignancies (s-AML; 14 of 29, 48.3%), as compared to de novo AML (30 of 131, 22.9%, P = .01). DAP-kinase hypermethylation in AML was associated with myelodysplastic changes in the bone marrow at the time of the initial diagnosis (P = .002) and with the presence of cytogenetic abnormalities (P = .02). Alteration in the apoptotic response due to the loss of DAP-kinase function may be an early event in the transformation pathway to secondary leukemia via myelodysplasia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Low level of DAP-kinase DNA methylation in myelodysplastic syndrome Kai Brakensiek, Florian Länger, Hans Kreipe, Ulrich Lehmann, Maria Teresa Voso, Alessandra Scardocci, Laura Valentini, Francesco Guidi, Stefan Hohaus, and Giuseppe Leone Blood 2004 104: 1586-1588. [Full Text] [PDF] This article has been cited by other articles: L. S. Kristensen and L. L. Hansen PCR-Based Methods for Detecting Single-Locus DNA Methylation Biomarkers in Cancer Diagnostics, Prognostics, and Response to Treatment Clin. Chem., August 1, 2009; 55(8): 1471 - 1483. [Abstract] [Full Text] [PDF] C S Chim, W W L Chan, and Y L Kwong Epigenetic dysregulation of the DAP kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in acute leukaemias J. Clin. Pathol., July 1, 2008; 61(7): 844 - 847. [Abstract] [Full Text] [PDF] M. Rizzi, M. P. Tschan, C. Britschgi, A. Britschgi, B. Hugli, T. J. Grob, N. Leupin, B. U. Mueller, H.-U. Simon, A. Ziemiecki, et al. The death-associated protein kinase 2 is up-regulated during normal myeloid differentiation and enhances neutrophil maturation in myeloid leukemic cells J. Leukoc. Biol., June 1, 2007; 81(6): 1599 - 1608. [Abstract] [Full Text] [PDF] N. J. Lacayo, J. F. DiMartino, M. C. Wei, and G. V. Dahl CpG Island Methylator Phenotype and Childhood Leukemia. Clin. Cancer Res., August 15, 2006; 12(16): 4787 - 4789. [Full Text] [PDF] G. Marcucci, C. D. Baldus, A. S. Ruppert, M. D. Radmacher, K. Mrozek, S. P. Whitman, J. E. Kolitz, C. G. Edwards, J. W. Vardiman, B. L. Powell, et al. Overexpression of the ETS-Related Gene, ERG, Predicts a Worse Outcome in Acute Myeloid Leukemia With Normal Karyotype: A Cancer and Leukemia Group B Study J. Clin. Oncol., December 20, 2005; 23(36): 9234 - 9242. [Abstract] [Full Text] [PDF] A. O. H. Nygren, N. Ameziane, H. M. B. Duarte, R. N. C. P. Vijzelaar, Q. Waisfisz, C. J. Hess, J. P. Schouten, and A. Errami Methylation-Specific MLPA (MS-MLPA): simultaneous detection of CpG methylation and copy number changes of up to 40 sequences Nucleic Acids Res., August 16, 2005; 33(14): e128 - e128. [Abstract] [Full Text] [PDF] J. C. Byrd, G. Marcucci, M. R. Parthun, J. J. Xiao, R. B. Klisovic, M. Moran, T. S. Lin, S. Liu, A. R. Sklenar, M. E. Davis, et al. A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia Blood, February 1, 2005; 105(3): 959 - 967. [Abstract] [Full Text] [PDF] K. Brakensiek, F. Langer, H. Kreipe, U. Lehmann, M. T. Voso, A. Scardocci, L. Valentini, F. Guidi, S. Hohaus, and G. Leone Low level of DAP-kinase DNA methylation in myelodysplastic syndrome Blood, September 1, 2004; 104(5): 1586 - 1588. [Full Text] [PDF] D. C. Malins, K. M. Anderson, N. L. Polissar, G. K. Ostrander, E. T. Knobbe, V. M. Green, N. K. Gilman, and J. L. Spivak Models of granulocyte DNA structure are highly predictive of myelodysplastic syndrome PNAS, April 6, 2004; 101(14): 5008 - 5011. [Abstract] [Full Text] [PDF]

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