SEARCH:   Advanced

Blood, 1 October 2009, Vol. 114, No. 14, pp. 2869-2877. Prepublished online as a Blood First Edition Paper on August 10, 2009; DOI 10.1182/blood-2009-03-212688. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2009-03-212688v1 114/14/2869    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 CrossRef Google Scholar Articles by de Jonge, H. J. M. Articles by Huls, G. PubMed PubMed Citation Articles by de Jonge, H. J. M. Articles by Huls, G. Related Collections Free Research Articles Myeloid Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS AML at older age: age-related gene expression profiles reveal a paradoxical down-regulation of p16INK4A mRNA with prognostic significance Hendrik J. M. de Jonge1, Eveline S. J. M. de Bont1, Peter J. M. Valk2, Jan Jacob Schuringa3, Marcel Kies3, Carolien M. Woolthuis3, Ruud Delwel2, Nic J. G. M. Veeger3,4, Edo Vellenga3, Bob Löwenberg2, and Gerwin Huls3 1 Division of Pediatric Oncology/Hematology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen; 2 Department of Hematology, Erasmus University Medical Center, Rotterdam; and Departments of 3 Hematology and 4 Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands Acute myeloid leukemia (AML) has a different clinical and biologic behavior in patients at older age. To gain further insight into the molecular differences, we examined a cohort of 525 adults to compare gene expression profiles of the one-third of youngest cases (n = 175; median age 31 years) with the one-third of oldest cases (n = 175; median age 59 years). This analysis revealed that 477 probe sets were up-regulated and 492 probe sets were down-regulated with increasing age at the significance level of P < .00001. After validation with 2 independent AML cohorts, the 969 differentially regulated probe sets on aging could be pointed to 41 probe sets, including the tumor-suppressor gene CDKN2A (encoding p16INK4A). In contrast to the induced p16INK4A expression that is associated with physiologic aging, p16INK4A is down-regulated in AML samples of patients with increasing age. However, this was only noticed in the intermediate- and unfavorable-risk group and not in the favorable-risk group and the molecularly defined subset "NPM1 mutant without FLT3-ITD." Multivariate analysis revealed p16INK4A, besides cytogenetic risk groups, as an independent prognostic parameter for overall survival in older patients. We conclude that, in addition to altered clinical and biologic characteristics, AML presenting at older age shows different gene expression profiles. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020