期刊
BRITISH JOURNAL OF CANCER
卷 97, 期 6, 页码 769-777出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6603951
关键词
Bfl-1; B-CLL; apoptosis; chemoresistance
类别
B-cell chronic lymphocytic leukaemia (B-CLL) is characterised by the progressive accumulation of monoclonal CD5(+) B cells. In a previous study, we have analysed the expression profile of apoptosis-regulating genes using a cDNA-based microarray and found overexpression of the antiapoptotic bcl-2 family member, bfl-1, in B-CLL cells with an apoptosis-resistant phenotype. In this study, bfl-1 mRNA levels have been determined by competitive PCR in an extended population of B-CLL patients to characterise its role in disease progression and development of chemoresistance. bfl-1 levels were significantly higher in patients with no response ( NR) to last chemotherapy than in patients responding ( partial response ( PR)) to last chemotherapy (P < 0.05) and in patients who had not required treatment (P < 0.05). We found no correlation between bfl-1 mRNA levels and disease progression, IGHV mutational status or other clinical parameters. In addition, bfl-1 mRNA levels were inversely correlated with apoptotic response to in vitro fludarabine treatment of B-CLL cells. Specific downregulation of bfl-1 using siRNA induced apoptosis in resistant cells. Our data suggest that bfl-1 contributes to chemoresistance and might be a therapeutic target in B-CLL.
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