Prognostic impact of apoptosis and proliferation in idiopathic (primary) myelofibrosis

A retrospective study of 120 patients with the clinically and histologicall y established diagnosis of idiopathic (primary) myelofibrosis (IMF) was per formed to determine prognostic factors of predictive value, including param eters characterizing the dynamics of hematopoietic cell kinetics. In contra st to previous studies, our cohort comprised the full, spectrum of the dise ase, from initial prefibrotic to advanced osteosclerotic stages. The in sit u end-labeling (ISEL) technique was used to demonstrate apoptosis, in order to determine dynamic parameters of predictive value. Cell proliferation wa s evaluated by employing the monoclonal antibody PC10 directed against prol iferating cell nuclear antigen (PCNA). Proliferative activity (PCNA index) and frequency of apoptosis showed significant differences between early and advanced fibrosclerotic stages of disease. Decrease in proliferation indic ated a significantly shorter survival, whereas a higher frequency of apopto tic cells was associated with a better prognosis. It may be speculated that a normal or enhanced proliferation rate expressed by PCNA positivity (late G(1)- and S-phase of the cell cycle) that is accompanied by a higher incid ence of apoptosis reflects the regenerative (turnover) capacity of hematopo iesis. This may apply especially to early hypercellular stages without rele vant myelofibrosis. In consideration of a recently published multivariate r isk model, a simplified synthesis score for stratification of a patient's p rognosis was constructed. Age, degree of anemia, leukocytes, and platelet c ount were regarded as the most important parameters. A substantial improvem ent of prognostic efficiency was further achieved by including PCNA index a nd frequency of apoptosis. Our results are in keeping with the assumption t hat generalization, indicated by myeloid metaplasia, has a prodigious impac t on prognosis in IMF. Furthermore, in this context dynamic features such a s proliferative activity and frequency of apoptosis exert an additional pre dictive value.