Fludarabine induces apoptosis in chronic lymphocytic leukemia - the role of P53, Bcl-2, Bax, Mcl-1, and Bag-1 proteins

Fludarabine induces apoptosis in chronic lymphocytic leukemia - the role of P53, Bcl-2, Bax, Mcl-1, and Bag-1 proteins

Author Faria, Jose Roberto de Autor UNIFESP Google Scholar
Yamamoto, Mihoko Autor UNIFESP Google Scholar
Faria, Rosa Malena Delbone de Autor UNIFESP Google Scholar
Kerbauy, José Autor UNIFESP Google Scholar
Oliveira, José Salvador Rodrigues de Autor UNIFESP Google Scholar
Institution Universidade Federal de Minas Gerais Hospital das Clínicas Serviço de Hematologia e Hemoterapia
Universidade Federal de São Paulo (UNIFESP)
Abstract 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.
Keywords Chronic lymphocytic leukemia
Apoptosis
Fludarabine
P53
Bcl-2
Bax
Mcl-1
Bag-1
Language English
Date 2006-03-01
Published in Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 39, n. 3, p. 327-333, 2006.
ISSN 0100-879X (Sherpa/Romeo, impact factor)
Publisher Associação Brasileira de Divulgação Científica
Extent 327-333
Origin http://dx.doi.org/10.1590/S0100-879X2006000300003
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000236565000003
SciELO ID S0100-879X2006000300003 (statistics in SciELO)
URI http://repositorio.unifesp.br/handle/11600/2942

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