Extensive apoptosis of bone marrow cells as evaluated by the in situ end-labelling (ISEL) technique may be the basis for ineffective haematopoiesis in patients with myelodysplastic syndromes

Apoptosis is a gene-directed cellular self-destruction which begins with in ternucleosomal cleavage of DNA and ends eventually with fragmentation of th e nucleus. We have shown that the technique of ISEL of fragmented DNA appea rs to be an accurate and reliable measurement of the early stages of apopto sis. The present study was undertaken in order to define the incidence of p rogrammed cell death in bone marrow (BM) haematopoietic and stromal cells o f myelodysplastic syndromes (MDS). The ISEL technique was employed in 21 BM biopsies of MDS patients. The analysis showed that in 11/21 patients, >70% cells (high score) were undergoing programmed cell death while 5 patients showed up to 1/3 of the biopsy containing apoptotic cells and 2 patients ha d only few occasional ISEL positive cells. Stromal cells including fat cell s, endothelial cells and fibroblasts were frequently in apoptosis in large clusters. Our results indicate that extensive apoptosis of haematopoietic c ells documented in BM biopsies of MDS patients may be the explanation for t he ineffective haematopoiesis which is the hallmark of these disorders.