Abstract |
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-gamma-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.
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Authors | 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, Jacqueline Boultwood |
Journal | Blood
(Blood)
Vol. 108
Issue 1
Pg. 337-45
(Jul 01 2006)
ISSN: 0006-4971 [Print] United States |
PMID | 16527891
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adaptor Proteins, Signal Transducing
- Antigens, CD34
- Interferons
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Topics |
- Adaptor Proteins, Signal Transducing
(genetics)
- Antigens, CD34
(genetics, metabolism)
- Bone Marrow Cells
(drug effects, metabolism, pathology)
- Gene Expression Profiling
- Humans
- Interferons
(pharmacology)
- International Cooperation
- Karyotyping
- Myelodysplastic Syndromes
(genetics)
- Phylogeny
- Reverse Transcriptase Polymerase Chain Reaction
(methods)
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