Expression of p53, bcl-2 and ras oncoproteins and apoptosis levels in acute leukaemias and myelodysplastic syndromes

We analysed by immunocytochemistry the expression of p53, bcl-2 and ras pro teins in bone marrow blasts from 59 patients with acute leukaemia (AL), 36 myeloid (AML) and 23 lymphoid (ALL), and from 22 patients with myelodysplas tic syndrome (MDS); our aim was to examine if abnormalities in their expres sion were associated with peculiar biological and clinical findings, or wit h an altered apoptosis rate, as measured by TUNEL technique. The oncoprotei ns were expressed with extreme variability, without significant differences among the various morphological or immunological AL subtypes. The mean per centages of bcl-2+ blasts were significantly higher in AML than in MDS (p = 0.01), and in MDS with bone marrow blastosis than in the forms without exc ess of blasts (p = 0.007). The lowest percentages of apoptotic cells were o bserved in ALL (mean 1%, p = 0.006), whereas in MDS the apoptotic index was higher (16.7%) than in AML (8.6%) and than in the normal controls (10.8%). but the difference tended to be statistically significant only for cases o f refractory anaemia. Whereas in AML and MDS the apoptotic rate was indepen dent of the oncoprotein expression, in ALL there was a significant linear r elationship between TUNEL and ras positivity (p = 0.01). Among AML patients treated with intensive polychemotherapy, no differences were observed in o ncoprotein expression and apoptotic rate between responders and resistant c ases. In conclusion, our data are in agreement with the hypothesis that dec reased apoptosis and enhanced cell survival are associated with AL, whereas a high level of apoptosis may be responsible for the ineffective hematopoi esis in MDS; abnormal expression of oncoproteins, even if not strictly rela ted to apoptosis level, may influence disease behaviour.