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Upregulation of bfl...
Upregulation of bfl-1 is a potential mechanism of chemoresistance in B-cell chronic lymphocytic leukaemia
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- Olsson, A. (author)
- Karolinska Institutet
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- Norberg, Maria (author)
- Uppsala universitet,Institutionen för genetik och patologi
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Ökvist, A. (author)
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Derkow, K. (author)
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- Choudhury, A. (author)
- Karolinska Institutet
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- Tobin, Gerard (author)
- Uppsala universitet,Institutionen för genetik och patologi
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Celsing, F. (author)
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- Österborg, A. (author)
- Karolinska Institutet
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- Rosenquist, Richard (author)
- Uppsala universitet,Institutionen för genetik och patologi
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- Jondal, M. (author)
- Karolinska Institutet
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- Osorio, L. M. (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2007-08-28
- 2007
- English.
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 97:6, s. 769-777
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https://www.nature.c...
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https://urn.kb.se/re...
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Abstract
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- 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.
Keyword
- Apoptosis
- B-CLL
- Bfl-1
- Chemoresistance
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Olsson, A.
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Norberg, Maria
-
Ökvist, A.
-
Derkow, K.
-
Choudhury, A.
-
Tobin, Gerard
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show more...
-
Celsing, F.
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Österborg, A.
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Rosenquist, Rich ...
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Jondal, M.
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Osorio, L. M.
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show less...
- Articles in the publication
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British Journal ...
- By the university
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Uppsala University
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Karolinska Institutet