EXPRESSION AND GENOMIC CONFIGURATION OF GM-CSF, IL-3, M-CSF RECEPTOR (C-FMS), EARLY GROWTH-RESPONSE GENE-1 (EGR-1) AND M-CSF GENES IN PRIMARY MYELODYSPLASTIC SYNDROMES

Peripheral blood mononuclear cells from seventeen patients with primar y myelodysplastic syndromes (MDS) in advanced stage were enriched for blasts and tested for (1) karyotype, (2) genomic configuration and (3) expression of IL-3, GM-CSF, FMS and EGR-1 genes which are all located on the long arm of chromosome 5. The expression of the M-CSF gene, th at has been recently reassigned to the short arm of chromosome 1 (1p), was also investigated. Aims of the study were to (1) assess the poten tial role of the expression of these genes in the maintenance and expa nsion of the neoplastic clones and (2) search for constitutional losse s or rearrangements of one allele followed by a deletion of the second allele of the same genes in the leukemic cells. The latter issue was investigated by comparing, in 8 cases, constitutive DNA from skin fibr oblasts with leukemic DNA. Eleven of the 17 patients had abnormal kary otypes. The M-CSF gene was expressed in 6 cases and the FMS and the EG R-1 genes were expressed in 2 of the latter cases. An autocrine mechan ism of growth could be hypothesized only for the 2 patients whose cell s expressed both the M-CSF and FMS genes. No germline changes or rearr angements were observed in any of the genes studied. Thus, deregulatio n of genes encoding for certain hemopoietic growth factors or receptor s does not seem to represent a major mechanism of MDS progression.