Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare subtype of leukemia/lymphoma, whose diagnosis can be difficult to achieve due to its clinical and biological heterogeneity, as well as its overlapping features with other hematologic malignancies. In this study we investigated whether the association between the maturational stage of tumor cells and the clinico-biological and prognostic features of the disease, based on the analysis of 46 BPDCN cases classified into three maturation-associated subgroups on immunophenotypic grounds. Our results show that blasts from cases with an immature plasmacytoid dendritic cell (pDC) phenotype exhibit an uncommon CD56− phenotype, coexisting with CD34+ non-pDC tumor cells, typically in the absence of extramedullary (e.g. skin) disease at presentation. Conversely, patients with a more mature blast cell phenotype more frequently displayed skin/extramedullary involvement and spread into secondary lymphoid tissues. Despite the dismal outcome, acute lymphoblastic leukemia-type therapy (with central nervous system prophylaxis) and/or allogeneic stem cell transplantation appeared to be the only effective therapies. Overall, our findings indicate that the maturational profile of pDC blasts in BPDCN is highly heterogeneous and translates into a wide clinical spectrum -from acute leukemia to mature lymphoma-like behavior-, which may also lead to variable diagnosis and treatment.
The aim of our study was to evaluate the benefits of supplementation with 800 mg/day of alpha-tocopherol with regard to cellular viability in HIV-1 seropositive patients undergoing anti-retroviral therapy. A total of 29 patients participated in the study, of whom 14 were given the supplement and 15 a placebo. The analyses were carried out before treatment commenced and after 60, 120 and 180 days. The plasma levels of HIV-1 RNA showed a significant decrease as a consequence of treatment time in the groups studied (p = 0.0001), although the difference between the treatments over time was not verified (p = 0.7343). The percentage of viable lymphocytes showed a significant increase as a consequence of treatment time in both groups studied (p = 0.0002) and a significant difference between the treatments over time (p = 0.0472). The percentage of lymphocytes in apoptosis showed a significant reduction over time (p = 0.0003), as well as a significant difference between the treatments over time (p = 0.0321). The significant increase in cellular viability indicates that supplementation with alpha-tocopherol offers an additional positive effect on cellular preservation in HIV-1 individuals undergoing anti-retroviral therapy; however, it represents an additional risk of anti-retroviral therapeutic failure, possibly due to drug-drug interaction involving up-regulation of metabolic clearance.
Evaluation of apoptosis by flow cytometry is generally accomplished by methods that use annexin V-FITC as vital dye, which access phosphatidylserine exposed on the external membrane at the beginning of this process. In addition, the concomitant use of propidium iodide makes possible to verify the characteristic nuclear alterations in the late stages of apoptosis, as a consequence of the increase in membrane permeability. On the other hand, the use of calcein-AM in association with ethidium homodimer (EthD-1) allows the evaluation of cell apoptosis through detection of esterase activity and cellular membrane physical and chemical alterations. The aim of this study was to compare the sensibility of calcein-AM and EthD-1 with annexin V-FITC and propidium iodide for early apoptosis evaluation in peripheral blood mononuclear cell culture, obtained from HIV-infected patients. Apoptosis and cellular viability were detected and quantified by flow cytometry after 24 and 48 hours incubation times. Our results showed that calcein-AM/EthD-1 was more sensitive for apoptotic cell quantification in both incubation times than annexin V-FITC/propidium iodide (mean of 46.95% ± 3.56, p < 0.0001, for 24 hours and mean of 37.67% ± 2.47, p < 0.0014 for 48 hours), besides allowing to clearly define viable, apoptotic and dead cell populations. Key-Words: Apoptosis, flow cytometry, annexin V, propidium iodide, calcein-AM, ethidium homodimer. Abbreviations: Calcein-AM, calcein acetoxymethyl ester; EthD-1, ethidium homodimer; FITC, fluorescein isothiocyanate.
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