Bortezomib induces different apoptotic rates in B-CLL cells according to IgVH and BCL-6 mutations
Clin. transl. oncol. (Print)
; 8(11): 805-811, nov. 2006. tab, ilus
Artigo
em Inglês
| IBECS
| ID: ibc-126237
Biblioteca responsável:
ES1.1
Localização: BNCS
ABSTRACT
BACKGROUND:
B-cell chronic lymphocytic leukemia (B-CLL) is a remarkably heterogeneous disorder. Some patients have an indolent disease whereas others undergo a more agressive presentation needing treatment. New therapeutics approaches are necessary for the treatment of B-CLL. Bortezomib (Btz), is a proteasome inhibitor, currently undergoing clinical trials whose function, at least in part, by stabilizing the IkappaBalpha protein and inhibiting NFkappaB activation.OBJECTIVE:
The objective of this work was to study the effects of Btz on isolated human B-CLL cells, in vitro, and to correlate the differential rates of apoptosis induction with biological variables. MATERIAL ANDMETHODS:
31 B-CLL samples, from patients in stage A of Binet were used for this study, and the apoptotic effect of Btz on these cells was measured.RESULTS:
Our data show that Btz treatment of B-CLL cells induces apoptosis in a time and dose-dependent manner. The apoptosis induction is mediated in part by inhibition of NFkappaB and is dependent on caspases activation. Interesting, in IgVH mutated cells, Btz have statistically significant differences in their in vitro activity on B-CLL cells according to their BCL-6 mutational status.CONCLUSIONS:
Btz is a promising pharmacologic agent for the treatment of B-CLL, but its efficacy seems to be related to IgVH and BCL-6 mutational status, therefore, it could be interesting to further investigate the mechanisms involved in the different behavior of the cells in response to apoptosis induction by this drug (AU)
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Espanha
Base de dados:
IBECS
Assunto principal:
Ácidos Bóricos
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NF-kappa B
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Apoptose
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Proteínas I-kappa B
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ADP-Ribosil Ciclase 1
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Quinase I-kappa B
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Antineoplásicos
Limite:
Adulto
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Idoso
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Feminino
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Humanos
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Masculino
Idioma:
Inglês
Revista:
Clin. transl. oncol. (Print)
Ano de publicação:
2006
Tipo de documento:
Artigo
Instituição/País de afiliação:
Hospital Clínico Universitario de Valencia/Spain
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Universidad de Valencia/Spain