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

Abstract

A retrospective study of 120 patients with the clinically and histologically established diagnosis of idiopathic (primary) myelofibrosis (IMF) was performed to determine prognostic factors of predictive value, including parameters characterizing the dynamics of hematopoietic cell kinetics. In contrast to previous studies, our cohort comprised the full spectrum of the disease, from initial prefibrotic to advanced osteosclerotic stages. The in situ end-labeling (ISEL) technique was used to demonstrate apoptosis, in order to determine dynamic parameters of predictive value. Cell proliferation was evaluated by employing the monoclonal antibody PC10 directed against proliferating 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 indicated a significantly shorter survival, whereas a higher frequency of apoptotic cells was associated with a better prognosis. It may be speculated that a normal or enhanced proliferation rate expressed by PCNA positivity (late G1- and S-phase of the cell cycle) that is accompanied by a higher incidence of apoptosis reflects the regenerative (turnover) capacity of hematopoiesis. This may apply especially to early hypercellular stages without relevant myelofibrosis. In consideration of a recently published multivariate risk model, a simplified synthesis score for stratification of a patient's prognosis was constructed. Age, degree of anemia, leukocytes, and platelet count were regarded as the most important parameters. A substantial improvement of prognostic efficiency was further achieved by including PCNA index and frequency of apoptosis. Our results are in keeping with the assumption that generalization, indicated by myeloid metaplasia, has a prodigious impact on prognosis in IMF. Furthermore, in this context dynamic features such as proliferative activity and frequency of apoptosis exert an additional predictive value.

Cadmium and copper reduce hematopoietic potential in common carp (Cyprinus carpio L.) head kidney

“…This caspase is commonly defined as effector caspase (Migliarini et al 2005). Evaluation of both precursor cell proliferation and apoptosis rate is applied in hematological studies to evaluate the rate of cell turnover and hematopoietic activity (Thiele et al 1997; Kvasnicka et al 1999). The presence of PCNA in fish hematopoietic tissue was confirmed by Leung et al (2005) for Danio rerio .…”

The Impact of Clinicopathological Studies on Staging and Survival in Essential Thrombocythemia, Chronic Idiopathic Myelofibrosis, and Polycythemia Rubra Vera

“…Unfortunately, risk classification of MPDs is mainly based on clinical data [5][6][7][8][9][10][11] and only a few clinical trials include explicitly BM biopsy examinations. 2,[12][13][14] Especially in those disorders associated with an elevated platelet count, differentiation between essential thrombocythemia (ET) and allied subtypes may be difficult without the possibility to recognize characteristic in relation with corresponding clinical data. 3 Regarding prognostic calculations in these cases, a most serious impairment is created by the failure to consider survival mortalities resulting from other causes than the underlying disorder, because in most studies only absolute (observed) survival rates have been calculated.…”

Classification of Ph-Negative Chronic Myeloproliferative Disorders – Morphology as the Yardstick of Classification

“…In univariate analysis, the prodromal phases show a more favorable survival in comparison with more advanced stages (MMM). However, in multivariate calculations, evolution of BM fibrosis displayed no significant influence on survival [84][85][86] .…”

“…Furthermore, it is important that in BM specimens maturation defects should be recognized in at least two lineages [82] , especially erythropoiesis and megakaryocytes (atypical micromegakaryocytes, abnormal nuclear lobulation, compact nuclei) [83] . Finally, although in the past decade many groups were engaged in the study of risk stratification and prognosis of CIMF patients, a comparison of these data reveals an extreme heterogeneity [84,85] . This result may be significantly influenced by including patients with PPMM into the corresponding calculations and the failure to recognize the prefibrotic and early stages of this disorder [58,85] .…”