Spontaneous apoptosis and proliferation detected by BCL-2 and CD71 proteins are important progression indicators within ZAP-70 negative chronic lymphocytic leukemia.
ABSTRACT In chronic lymphocytic leukemia (CLL), inhibition of spontaneous apoptosis determines a worse prognosis and increasing evidences show that disease progression relies also upon cycling CLL cells. We investigated bcl-2, as measure of apoptosis, and CD71, as measure of proliferation, by flow cytometry in 265 patients with CLL. Combining bcl-2 with CD71 values, we defined three subgroups: (1) bcl2 - CD71-; (2) bcl2 + CD71+; and (3) bcl2 + CD71- or bcl2- CD71+. Both a shorter progression-free survival (PFS) and overall survival (OS) were observed in ZAP-70+ (p < 0.00001) and in patients with bcl2 + CD71+ (p < 0.00001 and p = 0.02). The patients with discordant in bcl2 + CD71- and bcl2- CD71+ showed an intermediate outcome. Noteworthy, patients with bcl2 + CD71+ showed a shorter PFS within ZAP-70 negative subgroup (p = 0.00009). In multivariate analysis of PFS, age (p = 0.005), beta-(2) microglobulin (B(2)-M) (p = 0.003), bcl-2 (p = 0.004), CD49d (p = 0.001), and ZAP-70 (p < 0.001) resulted to be significant prognostic factors. The independent prognostic significance of B(2)-M (p = 0.009) and bcl-2 (p = 0.03) was confirmed within ZAP-70 negative patients. Bcl-2 and CD71 can be considered as interesting progression indicators, which should be validated in an independent cohort of patients, to take timely therapeutic decisions in CLL.
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ABSTRACT: Floating gastric adenocarcinoma cells in ascitic fluid are the main cause of peritoneal dissemination. Activation of apoptosis is an important mechanism by which tumor cells are eliminated by the immune surveillance system. Hence, we examined caspase-9 expression and the apoptosis in gastric adenocarcinoma cells in ascitic fluid using immunohistochemistry, real-time polymerase chain reaction and in situ cell death detection kits, flow cytometry. The results revealed strong expression of caspase-9 in 58.49% (31/53) malignant cells and a relatively weak expression of caspase-9 in 41.51% (22/53) malignant cells. The proportion of apoptotic cells in 31 malignant cases with strong caspase-9 expression (35.14 ± 3.42)% was significantly higher than that in 22 malignant cases with relatively weak caspase-9 expression (17.29 ± 7.62)% or in mesothelial cells (10.76 ± 4.21%; p < 0.05). Kaplan-Meier survival curves demonstrated that the patients with low caspase-9 expression showed significantly shorter survival (p < 0.05) than those with high caspase-9 expression. These findings suggest that immune clearance gastric carcinoma cells in ascites activated by caspase-9 helped to improve the prognosis of patients with gastric cancer.Apmis 03/2011; 119(3):173-9. · 2.07 Impact Factor
- 02/2012; , ISBN: 978-953-307-881-6
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ABSTRACT: Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in Western countries. Chromosomal abnormalities commonly found using conventional cytogenetics and FISH are del(11)(q22-23), trisomy 12, del(13)(q14), and del(17)(p13). Trisomy 12 is the most frequent numerical abnormality in CLL. It can appear isolated or associated with other chromosomal aberrations, including t(14;18)(q32;q21) and trisomy 18. The aim of this study was to determine whether CLL patients with isolated trisomy 12 or associated with other chromosomal alterations have different clinico-pathological features, including a different distribution NOTCH1 mutation. Patients were classified into four groups: Group 1, isolated trisomy 12 (n=14); Group 2, trisomy 12 plus trisomy 18 (n=4); Group 3, trisomy 12 plus t(14;18) (n=8); and Group 4: patients with trisomy 12 plus other abnormalities not involving BCL2 (n=28). The Binet stage and expression of ZAP70 were significantly different among cytogenetic groups. NOTCH1 mutations were detected in 6/12 (50%) patients from Group 1, 4/25 (16%) patients from Group 4, and in no patient from groups 2 and 3 (P=0.020). Patients in Group 2 had a more rapid disease progression (median Treatment-free Survival 2 months) as against patients from Groups 1 (50 months), 3 (69 months), or 4 (68 months; P=0.001). These findings indicate that the distribution of NOTCH1 mutations in CLL with trisomy 12 is heterogeneous and that the presence of additional chromosomal abnormalities such as trisomy 18 could change the prognosis of these patients.Genes Chromosomes and Cancer 05/2012; 51(9):881-9. · 3.55 Impact Factor