Bcl-2 and Bax expression and chlorambucil-induced apoptosis in the T-cellsand leukaemic B-cells of untreated B-cell chronic lymphocytic leukaemia patients

Citation
A. Thomas et al., Bcl-2 and Bax expression and chlorambucil-induced apoptosis in the T-cellsand leukaemic B-cells of untreated B-cell chronic lymphocytic leukaemia patients, LEUK RES, 24(10), 2000, pp. 813-821
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
LEUKEMIA RESEARCH
ISSN journal
0145-2126 → ACNP
Volume
24
Issue
10
Year of publication
2000
Pages
813 - 821
Database
ISI
SICI code
0145-2126(200010)24:10<813:BABEAC>2.0.ZU;2-R
Abstract
Chlorambucil and other cytotoxic drugs kill cells, non-selectively, by indu cing apoptosis. In this study, we measured the apoptotic response to chlora mbucil in T- and B-cells from untreated B-CLL patients and T-cells, from no rmal control subjects. We found increased chemosensitivity in the T-cells o f 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 decrea sing Bcl-2 expression with an elevated T-cell count. There was no different ial 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 ID50 values and both Bcl-2 expre ssion (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 che mosensitivity confirms a pivotal role for Bcl-2 in regulating a distal step in the apoptotic pathway following cytotoxic cellular damage. (C) 2000 Els evier Science Ltd. All rights reserved.