INCIDENCE AND ROLE OF APOPTOSIS IN MYELODYSPLASTIC SYNDROME - MORPHOLOGICAL AND ULTRASTRUCTURAL ASSESSMENT

By application of morphological and ultrastructural methods for identi fication of apoptosis, we analyzed the incidence of morphologically ev ident apoptosis in the bone marrow of 30 patients with myelodysplastic syndrome (MDS), and in the bone marrow of 12 healthy individuals. Acc ording to FAB classification, out of 30 patients, eight (26.6%) had re fractory anemia, three (10%) had refractory anemia with ringed siderob lasts, 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 apo ptosis were examined on semithin slides and expressed as the apoptotic index (Al) (percent counted on at least 1000 cells). An overall incre ase 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 patient s with evident karyotype changes Al was not higher than in patients wi th normal karyotype. This suggests that discrete alterations in apopto sis are present even in karyotypically 'normal' clones. Our results st rongly support the hypothesis that apoptosis has a role in ineffective hematopoiesis and may be a mechanism responsible for the paradox of h ypercellular bone marrow and peripheral blood pancytopenia in MDS.