What does apoptosis have to do with clinical features in myelodysplastic syndrome?

Abstract

BACKGROUND AND OBJECTIVES: Apoptosis is thought to play a key pathogenic role in myelodysplastic syndrome. The aim of our study was to determine whether apoptotic index, p53 and bcl-2 levels correlate with the clinical consequences of ineffective hematopoiesis; namely, the development of cytopenia and the shortened survival of patients with myelodysplastic syndrome. DESIGN AND METHODS: The apoptotic index, determined by TdT-mediated dUTP nick-end labeling, as well as bcl-2 and p53 protein levels, evaluated by immunohistochemistry, were studied in bone marrow trephine biopsy archival samples from 25 healthy subjects aged over fifty (control group), 61 consecutive patients with myelodysplastic syndrome and 17 patients with de novo acute myeloid leukemia according to FAB criteria. The correlation between relevant clinical parameters was analyzed with Spearman's correlation test. Factors influencing survival were studied by Cox proportional hazards regression analysis. RESULTS: The apoptotic index did not correlate with blood counts at diagnosis and had no prognostic influence on the overall survival of patients with myelodysplastic syndrome. The p53 score correlated with both the leukocyte count (r=-0.274, p=0.034, Spearman's) and hemoglobin concentration (r=-0.316; p=0.014) in the myelodysplastic syndrome patients and showed an independent and significant prognostic influence on their overall survival (p=0.045, Cox's) while the bcl-2 score was not correlated with their blood counts or prognosis. INTERPRETATION AND CONCLUSIONS: Apoptotic index and bcl-2 do not correlate with key clinical data in patients with myelodysplastic syndrome, while p53 levels show a good correlation with these data and may be a useful parameter to add to current prognostic schemes in this entity.