Juha Ollila | PubMed Health

PubMed2002

Microarray analysis of B-cell stimulation.

B-cell development to antibody-producing plasma cells requires the concerted function of a large number of genes and proteins. Genome-level expression profiling during human B-cell maturation was studied in anti-immunoglobulin M-stimulated Ramos cells. cDNA microarrays were used to follow changes in the transcriptome over several days. Close to 1500 genes had significantly altered expression at least at one time point. The genes were organized into clusters based on expression profiles and were further characterized based on the functions of the coded proteins. Several groups of genes important for B cells were analyzed. Here we concentrate on genes involved in signal transduction and cytokines and their receptors. The results provide knowledge on the development of humoral immunity. Several new genes were found to be essential for B-cell development. They can be used as targets for research and possibly for drug development.

Antibody Formation↗

PubMed2002

Overexpression of translocation-associated fusion genes of FGFRI, MYC, NPMI, and DEK, but absence of the translocations in acute myeloid leukemia. A microarray analysis.

BACKGROUND AND OBJECTIVES: Translocation-associated gene fusions are well recognized in acute myeloid leukemia. Other molecular genetic changes are less well known. The novel cDNA technology has opened the avenue to large-scale gene expression analysis. Our aim was to perform cDNA microarray analysis of acute myeloid leukemia (AML). DESIGN AND METHODS: We performed cDNA microarray analysis using the Clontech hematology filter (containing 406 genes) on 15 patients to study gene expression profiling in AML. As reference, we used whole bone marrow from 5 healthy donors. RESULTS: Our results revealed 50 differentially expressed genes in at least 3 out of 15 patients. Twenty-two genes were upregulated (ratio > or =4), whereas 28 genes were downregulated (ratio < or =0.25). All but one of the 13 genes tested by real-time polymerase chain reaction (PCR) showed the same expression profiles. Among the overexpressed genes, several were those earlier associated with chromosomal translocations and gene fusions. These genes were FGFR1, MYC, NPM1, DEC, and BCL2. The expression of two upregulated genes, HOXA4 and CSF1R, was significantly higher in patients with a white blood cell count higher than 30 x 10(9)/L cells. In patients whose white blood cell count was higher than 100 x 10(9)/L cells, both CLC and GRN were significantly underexpressed, whereas HOXA4 and DAPK1 were overexpressed. FGFR1 and CAMLG were more frequently significantly overexpressed in patients with CD56 immunophenoytpe. INTERPRETATION AND CONCLUSIONS: Clinical and prognostic significance of differential gene expression should be studied with a larger series of patients by using other techniques, such as quantitative real-time PCR.

Acute Disease↗