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

Aims: To investigate the ultrastructural characteristics of erythroblasts i n myelodysplasia (MDS) which might be of additional importance in understan ding its pathogenesis. Methods and results: 22 patients were classified acc ording to FAB (French-American-British classification), IPSS (international prognostic score system), cytogenetic risk factors and transfusion depende ncy. Using electron microscopy, in 77% of the cases, nuclear abnormalities consisting of disrupted membranes and cystic/dilated perinuclear spaces wer e noted. In a limited number of patients (n = 7), a low percentage of apopt osis in the erythroid lineage (mean 3.1 +/- 1.6%; median 3%: range 1-6) (no rmal controls: < 0.5%) could be noted, primarily in mature erythroblasts an d significantly associated with spongiform nuclear features. In all patient s extensive cytoplasmic vacuolization and myelin figures in erythroblasts w ere demonstrated. In 55% of the cases, enlarged and abnormal mitochondria w ere observed, significantly associated with iron-accumulation. A significan t inverse relation existed between the absence of apoptosis and more advanc ed, or high risk disease and cytogenetic risk factors. Mitochondrial abnorm alities were significantly correlated with high risk disease as well with a n increase in transfusion dependency. Conclusions: These data indicate that in MDS apoptosis may play a role in early stages of disease. The overall p rominent defects in mitochondria might be an additional defect that is invo lved in ineffective erythropoiesis. <(c)> 2001 Elsevier Science Ltd. All ri ghts reserved.