Apoptosis, bcl-2 expression and p53 accumulation in myelodysplastic syndrome, myelodysplastic-syndrome-derived acute myelogenous leukemia and de novoacute myelogenous leukemia

Apoptosis and its dysregulation have been implicated in dysplastic and inef fective hematopoiesis and the neoplastic transformation of bone marrow in m yelodysplastic syndrome (MDS). To explore the role of apoptosis in hematolo gical disorders, we examined the frequency of apoptotic cells by the in sit u end labeling method in bone marrow specimens from 37 patients with MDS [r efractory anemia (RA) 10 cases, RA with excess of blasts (RAEB) 27 cases in cluding 12 cases with leukemic transformation], 12 patients with MDS-derive d acute myelogenous leukemia (AML) and 13 patients with de novo AML. In add ition, we investigated the relationship of apoptosis to the immunohistochem ical expression of bcl-2 and p53 in these cases, and the association of apo ptosis, bcl-2, and p53 with the leukemic evolution of MDS by examining sequ ential bone marrow samples of the same patient from the time of initial dia gnosis to the time of overt leukemia. The percentage frequency of apoptotic cells was significantly greater in MDS (RA: 9.46 +/- 2.99%, m +/- SD; RAEB : 5.60 +/- 3.09) as compared with those in MDS-derived AML (0.62 +/- 0.37), de novo AML (0.28 +/- 0.11) and controls (1.00 +/- 0.59). On the other han d, the cases of RAEB with leukemic transformation exhibited a lower frequen cy of apoptotic cells and a higher frequency of bcl-2- and p53-positive cel ls than those without transformation. When the RAEB cases transformed to AM L, the frequency of apoptotic cells was significantly reduced (2.96 +/- 1.5 4 --> 0.62 +/- 0.37), while the frequencies of bcl-2-positive cells and p53 -positive cells were greater (10.88 +/- 3.66 --> 30.54 +/- 7.14, and 20.21 +/- 6.21 --> 32.34 +/- 14.71, respectively). In contrast to MDS-derived AML , over a half of de novo AML cases showed few p53-positive cells. These fin dings corroborate the earlier notion that apoptosis may play a substantial role in dysplastic and ineffective hematopoiesis in MDS. It is also suggest ed that the suppression of apoptosis associated with enhanced bcl-2 express ion and p53 accumulation increases the probability of developing leukemia i n MDS, and that oncogenetic development might be different between MDS-deri ved AML and de novo AML. Copyright (C) 2000 S. Karger AG, Basel.