Gene expression profiling in the myelodysplastic syndromes using cDNA microarray technology

• Published in: British journal of haematology Vol. 125; no. 5; pp. 576 - 583
• Main Authors: Pellagatti, Andrea, Esoof, Noor, Watkins, Fiona, Langford, Cordelia F., Vetrie, David, Campbell, Lisa J., Fidler, Carrie, Cavenagh, James D., Eagleton, Helen, Gordon, Peter, Woodcock, Barrie, Pushkaran, Beena, Kwan, Mark, Wainscoat, James S., Boultwood, Jacqueline
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.06.2004; Blackwell; Blackwell Publishing Ltd
• Subjects: 5q‐ syndrome; acute myeloid leukaemia; Biological and medical sciences; cDNA microarray; Down-Regulation; expression profiling; Gene Expression Profiling - methods; Hematologic and hematopoietic diseases; Hematology; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Multigene Family; Myelodysplastic syndromes; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - pathology; Neutrophils - pathology; Oligonucleotide Array Sequence Analysis - methods; Reverse Transcriptase Polymerase Chain Reaction - methods; Up-Regulation; Hematology; Acute; expression profiling; DNA chip; cDNA microarray; Malignant hemopathy; Chromosome B5; Myelodysplastic syndrome; Gene expression profile; Complementary DNA; Gene; Technology; 5q- syndrome; acute myeloid leukaemia; myelodysplastic syndromes; Acute myelocytic leukemia
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2004.04958.x

Summary 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.