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Blood, 1 July 2006, Vol. 108, No. 1, pp. 337-345.
Prepublished online as a Blood First Edition Paper on March 9, 2006; DOI 10.1182/blood-2005-12-4769.
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NEOPLASIA
Gene expression profiles of CD34+ cells in myelodysplastic syndromes: involvement of interferon-stimulated genes and correlation to FAB subtype and karyotype
Andrea Pellagatti,
Mario Cazzola,
Aristoteles A. N. Giagounidis,
Luca Malcovati,
Matteo G. Della Porta,
Sally Killick,
Lisa J. Campbell,
Li Wang,
Cordelia F. Langford,
Carrie Fidler,
David Oscier,
Carlo Aul,
James S. Wainscoat, and
Jacqueline Boultwood
From the Leukaemia Research Fund (LRF) Molecular Haematology Unit, Nuffield Department of Clinical Laboratory Sciences (NDCLS), John Radcliffe Hospital, Oxford, United Kingdom; the Division of Hematology, University of Pavia Medical School, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, Italy; the Medizinische Klinik II, St Johannes Hospital, Duisburg, Germany; the Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom; and the Microarray Facility, The Sanger Institute, Hinxton, Cambridge, United Kingdom.
To gain insight into the poorly understood pathophysiology of the myelodysplastic syndromes (MDSs), we have determined the gene expression profiles of the CD34+ cells of 55 patients with MDS by using a comprehensive array platform. These profiles showed many similarities to reported interferon- -induced gene expression in normal CD34+ cells; indeed the 2 most up-regulated genes, IFIT1 and IFITM1, are interferon-stimulated genes (ISGs). Alterations in the expression of ISGs may play a role in the hematologic features of MDS, such as peripheral blood cytopenias. Up-regulation of IFIT1 is a potential diagnostic marker for MDS. We determined whether distinct gene expression profiles were associated with specific FAB and cytogenetic groups. CD34+ cells from patients with refractory anemia with ringed sideroblasts (RARS) showed a particular gene expression profile characterized by up-regulation of mitochondrial-related genes and, in particular, of those of heme synthesis (eg, ALAS2). CD34+ cells from patients with the del(5q) had a distinct gene expression profile, characterized by down-regulation of genes assigned to 5q, and up-regulation of the histone HIST1 gene cluster at chromosome 6p21 and of genes related to the actin cytoskeleton. This study provides important and new insights into the pathophysiology of MDS. (Blood. 2006;108:337-345)
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