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Blood, 1 October 2009, Vol. 114, No. 14, pp. 2969-2983. Prepublished online as a Blood First Edition Paper on July 16, 2009; DOI 10.1182/blood-2008-08-175091. This Article Full Text Full Text (PDF) Supplemental Methods, Tables, and Figure All Versions of this Article: blood-2008-08-175091v1 114/14/2969    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 Ravoet, M. Articles by Willard-Gallo, K. PubMed PubMed Citation Articles by Ravoet, M. Articles by Willard-Gallo, K. Related Collections Immunobiology Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Molecular profiling of CD3–CD4+ T cells from patients with the lymphocytic variant of hypereosinophilic syndrome reveals targeting of growth control pathways Marie Ravoet1,2, Catherine Sibille2, Chunyan Gu1, Myriam Libin1,3, Benjamin Haibe-Kains4,5, Christos Sotiriou4, Michel Goldman3, Florence Roufosse3, and Karen Willard-Gallo1 1 Molecular Immunology Unit, Institut Jules Bordet, Université Libre de Bruxelles, Brussels; 2 Center for Human Genetics, Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels; 3 Department of Internal Medecine, Hôpital Erasme, Brussels and Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies; 4 Functional Genomics Unit, Institut Jules Bordet, Université Libre de Bruxelles, Brussels; and 5 Machine Learning Group, Computer Science Department, Université Libre de Bruxelles, Brussels, Belgium The clonal CD3–CD4+ T-cell population characterizing lymphocytic variant hypereosinophilic syndrome (L-HES) persists for years, with a subgroup of patients ultimately progressing to T lymphoma. The molecular changes associated with the premalignant clone and the emergence of malignant subclones are unknown, precluding the development of targeted therapy for this HES variant. In this study, we used whole genome arrays to examine gene expression in the CD3–CD4+ T cells and found that 850 genes were differentially regulated during chronic disease compared with CD3+CD4+ T cells from healthy donors. Changes in the expression of 349 genes were altered in association with the clinical progression from chronic L-HES to T lymphoma in 1 patient, with 87 of 349 genes representing further changes in genes whose expression was altered in all chronic disease patients (87 of 850). Array analysis after CD2/CD28-mediated activation revealed that the major gene expression changes observed in the CD3–CD4+ T cells do not reflect activation induced alterations but rather pathways involved in T-cell homeostasis, including transforming growth factor-β signaling, apoptosis, and T-cell maturation, signaling, and migration. Examination of microRNA expression in the CD3–CD4+ T cells from patients with chronic disease identified 23 microRNAs that changed significantly, among which miR-125a further decreased in association with one patient's evolution to T lymphoma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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