Mitochondrial disruption and limited apoptosis of erythroblasts are associated with high risk myelodysplasia. An ultrastructural analysis

Abstract

Aims: To investigate the ultrastructural characteristics of erythroblasts in myelodysplasia (MDS) which might be of additional importance in understanding its pathogenesis. Methods and results: 22 patients were classified according to FAB (French–American–British classification), IPSS (international prognostic score system), cytogenetic risk factors and transfusion dependency. Using electron microscopy, in 77% of the cases, nuclear abnormalities consisting of disrupted membranes and cystic/dilated perinuclear spaces were noted. In a limited number of patients ( n=7), a low percentage of apoptosis in the erythroid lineage (mean 3.1±1.6%; median 3%: range 1–6) (normal controls: <0.5%) could be noted, primarily in mature erythroblasts and significantly associated with spongiform nuclear features. In all patients extensive cytoplasmic vacuolization and myelin figures in erythroblasts were demonstrated. In 55% of the cases, enlarged and abnormal mitochondria were observed, significantly associated with iron-accumulation. A significant inverse relation existed between the absence of apoptosis and more advanced, or high risk disease and cytogenetic risk factors. Mitochondrial abnormalities were significantly correlated with high risk disease as well with an increase in transfusion dependency. Conclusions: These data indicate that in MDS apoptosis may play a role in early stages of disease. The overall prominent defects in mitochondria might be an additional defect that is involved in ineffective erythropoiesis.