Bcl-2 and bax expression and chlorambucil-induced apoptosis in the T-cells and leukaemic B-cells of untreated B-cell chronic lymphocytic leukaemia patients.
Leuk Res
; 24(10): 813-21, 2000 Oct.
Article
em En
| MEDLINE
| ID: mdl-10996199
ABSTRACT
Chlorambucil and other cytotoxic drugs kill cells, non-selectively, by inducing apoptosis. In this study, we measured the apoptotic response to chlorambucil in T- and B-cells from untreated B-CLL patients and T-cells, from normal control subjects. We found increased chemosensitivity in the T-cells of B-CLL patients compared to the controls (P=0.0002). The chlorambucil ID(50) values for T-cells from B-CLL patients showed a direct correlation with Bcl-2 expression (P=0.002) and an inverse correlation with CD3 cell count (P<0.0001), suggesting a trend of increasing chemosensitivity and decreasing Bcl-2 expression with an elevated T-cell count. There was no differential expression of Bcl-2 or Bax between the CD4(+) and CD8(+) cells of B-CLL patients, isolated by immunomagnetic separation. We found correlations in the leukaemic B-cells between chlorambucil ID(50) values and both Bcl-2 expression (P=0.006), and Bcl-2/Bax ratios (P=0.002), suggesting a role for the Bcl-2/Bax ratio in predicting the response of untreated CLL patients to cytotoxic treatment. Chlorambucil produced almost identical changes in Bcl-2 and Bax expression in normal T-cells and leukaemic B-cells triggered to die by apoptosis, which together with the correlation between Bcl-2 and chemosensitivity confirms a pivotal role for Bcl-2 in regulating a distal step in the apoptotic pathway following cytotoxic cellular damage.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
/
Linfócitos T
/
Leucemia Linfocítica Crônica de Células B
/
Clorambucila
/
Proteínas Proto-Oncogênicas
/
Apoptose
/
Antineoplásicos Alquilantes
/
Proteínas Proto-Oncogênicas c-bcl-2
Limite:
Humans
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article