Incidence and role of apoptosis in myelodysplastic syndrome: morphological and ultrastructural assessment

By application of morphological and ultrastructural methods for identification of apoptosis, we analyzed the incidence of morphologically evident apoptosis in the bone marrow of 30 patients with myelodysplastic syndrome (MDS), and in the bone marrow of 12 healthy individuals. According to FAB classification, out of 30 patients, eight (26.6%) had refractory anemia, three (10%) had refractory anemia with ringed sideroblasts, 14 (46.6%) had refractory anemia with excess of blasts and two (6.8%) had refractory anemia with excess of blasts in transformation. Three patients (10%) had chronic myelomonocytic leukemia. Cells in apoptosis were examined on semithin slides and expressed as the apoptotic index (Al) (percent counted on at least 1000 cells). An overall increase in apoptosis in patients with MDS was found (median Al in patients vs controls, 3.13% vs 1.05%, P < 0.01 by Rilann-Whitney U test). Also, negative correlation between Al and white blood cell count was found (linear r=-0.53, or Spearman rank R=-0.52, both P < 0.01). In patients with evident karyotype changes Al was not higher than in patients with normal karyotype. This suggests that discrete alterations in apoptosis are present even in karyotypically 'normal' clones. Our results strongly support the hypothesis that apoptosis has a role in ineffective hematopoiesis and may be a mechanism responsible for the paradox of hypercellular bone marrow and peripheral blood pancytopenia in MDS.