1. ¹Department of Tumor and Cell Biology, Karolinska Institutet, Stockholm 17177, Sweden
2. ²Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala 75185, Sweden
3. ³Department of Clinical Neuroscience, Karolinska University Hospital, Stockholm 17176, Sweden
4. ⁴Department of Oncology–Pathology, Karolinska Institutet, Stockholm 17177, Sweden
5. ⁵Departments of Hematology and Oncology, Karolinska University Hospital, Stockholm 17176, Sweden

Correspondence: Dr LM Osorio, E-mail: lyda.osorio@ki.se

Received 21 May 2007; Revised 31 July 2007; Accepted 1 August 2007; Published online 28 August 2007.

Abstract

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.