Bcl-2 expression in myelodysplastic syndrome

D.S. Marta a, A. Moicean MD, b, E. Moldoveanu PhD a

a National Institute of Research and Developement in Pathology and Biomedical Sciences- "Victor Babes", Ultrastructural Pathology Department, Bucharest, Romania b Fundeni Hospital, Department of Hematology, Bucuresti, Romania

The myelodysplastic syndrome (MDS) is a heterogenous group of clonal stem cell disorders (refractory anemia-RA, refractory anemia with ringed sideroblasts-RARS, refractory anemia with excess of blasts-RA EB, refractory anemia with excess of blasts with transformation-RAEB-t, chronic myelomonocytic leukemia-CMML) characterized by trilineage dysplasia, peripheral pancytopenia and normo- or hypercellular bone marrow (BM) and an approximately 30% incidence of eventual transformation into acute myeloid leukemia (AML). Recent data have provided evidence supporting the hypothesis that increased levels of apoptosis occur early in MDS bone marrow cells, but then diminish as the disease progress. We have studied Bcl-2 a protein with antiapoptotic and antioxidant potential, and its expression in hematopoietic cells is inversely related to maturation. For the ultrastructural investigation of BM samples we have worked with usual electron microscopy techniques. Electron microscopy revealed that the majority of hematopoietic cell in the BM had ultrastructural feature of various stages of apoptosis ranging from margination and condendensation of nuclear chromatin to full nuclear pyknosis and vacuolization of the cytoplasm, with polarization of the organelles. For the quantitative determinations of Bcl-2 in the BM aspirate we worked with peroxidase labeled anti-Bcl-2 monoclonal antibodies, 2,2'-azino-bis (3-ethylbenz-thiazoline-6-sulfonic acid) (ABTS) being peroxidase substrate. Peroxidase activity was quantitatively estimated by spectrophotometric activity at 415 nm. The bcl-2 expression in myelodysplastic cells is inversely correlated with the rate of cells' apoptosis. RA < RAEB < RAEB-t < AML-MDS The suppression of apoptosis in cases with leukemic transformation is associated with enhanced bcl-2 expression.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Apoptosis - Molecular Mechanisms.