title: Gene expression profiling in the myelodysplastic syndromes using cDNA microarray technology.
abstract: The myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal disorders of the haematopoietic stem cell and primarily involve cells of the myeloid lineage. Using cDNA microarrays comprising 6000 human genes, we studied the gene expression profiles in the neutrophils of 21 MDS patients, seven of which had the 5q- syndrome, and two acute myeloid leukaemia (AML) patients when compared with the neutrophils from pooled healthy controls. Data analysis showed a high level of heterogeneity of gene expression between MDS patients, most probably reflecting the underlying karyotypic and genetic heterogeneity. Nevertheless, several genes were commonly up or down-regulated in MDS. The most up-regulated genes included RAB20, ARG1, ZNF183 and ACPL. The RAB20 gene is a member of the Ras gene superfamily and ARG1 promotes cellular proliferation. The most down-regulated genes include COX2, CD18, FOS and IL7R. COX2 is anti-apoptotic and promotes cell survival. Many genes were identified that are differentially expressed in the different MDS subtypes and AML. A subset of genes was able to discriminate patients with the 5q- syndrome from patients with refractory anaemia and a normal karyotype. The microarray expression results for several genes were confirmed by real-time quantitative polymerase chain reaction. The MDS-specific expression changes identified are likely to be biologically important in the pathophysiology of this disorder.
authors.affiliation: Leukaemia Research Fund Molecular Haematology Unit, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pellagatti
authors.forename: Noor
authors.initials: N
authors.lastname: Esoof
authors.forename: Fiona
authors.initials: F
authors.lastname: Watkins
authors.forename: Cordelia F
authors.initials: CF
authors.lastname: Langford
authors.forename: David
authors.initials: D
authors.lastname: Vetrie
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Campbell
authors.forename: Carrie
authors.initials: C
authors.lastname: Fidler
authors.forename: James D
authors.initials: JD
authors.lastname: Cavenagh
authors.forename: Helen
authors.initials: H
authors.lastname: Eagleton
authors.forename: Peter
authors.initials: P
authors.lastname: Gordon
authors.forename: Barrie
authors.initials: B
authors.lastname: Woodcock
authors.forename: Beena
authors.initials: B
authors.lastname: Pushkaran
authors.forename: Mark
authors.initials: M
authors.lastname: Kwan
authors.forename: James S
authors.initials: JS
authors.lastname: Wainscoat
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Boultwood
mesh_terms: D015536:Down-Regulation; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D005810:Multigene Family; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology; D009504:Neutrophils / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015854:Up-Regulation