RESUMO
The expression of P53, Bcl-2, Bax, Bag-1, and Mcl-1 proteins in CD5/CD20-positive B-chronic lymphocytic leukemia (B-CLL) cells from 30 typical CLL patients was evaluated before and after 48 h of incubation with 10-6 M fludarabine using multiparametric flow cytometric analysis. Protein expression was correlated with annexin V expression, Rai modified clinical staging, lymphocyte doubling time, and previous treatment. Our main goal was to determine the predictive value of these proteins in CLL cells in terms of disease evolution. Bcl-2 expression decreased from a median fluorescence index (MFI) of 331.71 ± 42.2 to 245.81 ± 52.2 (P < 0.001) after fludarabine treatment, but there was no difference between viable cells (331.57 ± 44.6 MFI) and apoptotic cells (331.71 ± 42.2 MFI) before incubation (P = 0.859). Bax expression was higher in viable cells (156.24 ± 32.2 MFI) than in apoptotic cells (133.56 ± 35.7 MFI) before incubation, probably reflecting defective apoptosis in CLL (P = 0.001). Mcl-1 expression was increased in fludarabine-resistant cells and seemed to be a remarkable protein for the inhibition of the apoptotic process in CLL (from 233.59 ± 29.8 to 252.04 ± 35.5; P = 0.033). After fludarabine treatment, Bag-1 expression was increased in fludarabine-resistant cells (from 425.55 ± 39.3 to 447.49 ± 34.5 MFI, P = 0.012), and interestingly, this higher expression occurred in patients who had a short lymphocyte doubling time (P = 0.022). Therefore, we could assume that Bag-1 expression in such situation might identify CLL patients who will need treatment earlier.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apoptose , Antineoplásicos/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Leucemia Linfocítica Crônica de Células B/metabolismo , Proteínas de Neoplasias/metabolismo , Vidarabina/análogos & derivados , Proteínas de Ligação a DNA/metabolismo , Citometria de Fluxo , Leucemia Linfocítica Crônica de Células B/fisiopatologia , /metabolismo , Fatores de Transcrição/metabolismo , /metabolismo , Vidarabina/farmacologia , /metabolismoRESUMO
The expression of P53, Bcl-2, Bax, Bag-1, and Mcl-1 proteins in CD5/CD20-positive B-chronic lymphocytic leukemia (B-CLL) cells from 30 typical CLL patients was evaluated before and after 48 h of incubation with 10(-6) M fludarabine using multiparametric flow cytometric analysis. Protein expression was correlated with annexin V expression, Rai modified clinical staging, lymphocyte doubling time, and previous treatment. Our main goal was to determine the predictive value of these proteins in CLL cells in terms of disease evolution. Bcl-2 expression decreased from a median fluorescence index (MFI) of 331.71 +/- 42.2 to 245.81 +/- 52.2 (P < 0.001) after fludarabine treatment, but there was no difference between viable cells (331.57 +/- 44.6 MFI) and apoptotic cells (331.71 +/- 42.2 MFI) before incubation (P = 0.859). Bax expression was higher in viable cells (156.24 +/- 32.2 MFI) than in apoptotic cells (133.56 +/- 35.7 MFI) before incubation, probably reflecting defective apoptosis in CLL (P = 0.001). Mcl-1 expression was increased in fludarabine-resistant cells and seemed to be a remarkable protein for the inhibition of the apoptotic process in CLL (from 233.59 +/- 29.8 to 252.04 +/- 35.5; P = 0.033). After fludarabine treatment, Bag-1 expression was increased in fludarabine-resistant cells (from 425.55 +/- 39.3 to 447.49 +/- 34.5 MFI, P = 0.012), and interestingly, this higher expression occurred in patients who had a short lymphocyte doubling time (P = 0.022). Therefore, we could assume that Bag-1 expression in such situation might identify CLL patients who will need treatment earlier.
Assuntos
Antineoplásicos/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Apoptose , Leucemia Linfocítica Crônica de Células B/metabolismo , Proteínas de Neoplasias/metabolismo , Vidarabina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Ligação a DNA/metabolismo , Feminino , Citometria de Fluxo , Humanos , Leucemia Linfocítica Crônica de Células B/fisiopatologia , Masculino , Pessoa de Meia-Idade , Proteína de Sequência 1 de Leucemia de Células Mieloides , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Vidarabina/farmacologia , Proteína X Associada a bcl-2/metabolismoRESUMO
CONTEXT: Chronic lymphocytic leukemia (CLL) is a clonal lymphoproliferative disorder, characterized by B lymphocytic proliferation. CLL is the most frequent adult leukemia in Western countries, accounting for 25 to 30% of all white leukemic patients. OBJECTIVE: To evaluate clinical and staging characteristics in prognosis of chronic lymphocytic leukemia. DESIGN: Evaluation of clinical-staging data. SETTING: Universidade Federal de São Paulo - Escola Paulista de Medicina / Universidade de Alfenas. SAMPLE: 73 patients diagnosed from 1977 to 1994. MAIN MEASUREMENTS: Sex, ethnic origin, age, lymphadenopathy, splenomegaly, hepatomegaly, three or more areas of lymphoid enlargement, hemoglobin (g/dl), lymphocytes/mm3, Platelets/mm3 RESULTS: Mean survival of patients was 76 months, median age was 65 years, ranging from 33 to 87. Forty-four patients (60.3%) were male and 29 (39.7%) female. CONCLUSION: The Binet system determined a better prognosis than Rai.
