Bcl-2 family gene modulation during spontaneous apoptosis of B-chronic lymphocytic leukemia cells

Malignant cell accumulation in B-cell chronic lymphocytic leukemia (B-CLL) is primarily caused by defective apoptosis rather than increased proliferation. To further understand the role of Bcl-2 family members, known regulators of apoptosis, in the abnormal B-CLL survival, we have measured their mRN...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2004-03, Vol.315 (3), p.562-567
Main Authors: Sanz, Laura, Garcia-Marco, José A, Casanova, Benito, de la Fuente, Marı́a Teresa, Garcı́a-Gila, Mercedes, Garcia-Pardo, Ángeles, Silva, Augusto
Format: Article
Language:English
Subjects:
Apoptosis
Apoptosis - genetics
Apoptosis Regulatory Proteins
B-CLL
B-Lymphocytes - metabolism
Bcl-2 family
Bik
Cell Line, Tumor
Female
Gene Expression Profiling - methods
Gene Expression Regulation, Leukemic
Genes, bcl-2
Humans
Leukemia, Lymphocytic, Chronic, B-Cell - genetics
Leukemia, Lymphocytic, Chronic, B-Cell - metabolism
Leukemia, Lymphocytic, Chronic, B-Cell - pathology
Male
Membrane Proteins - biosynthesis
mRNA expression
Neoplasm Staging
Proto-Oncogene Proteins c-bcl-2 - biosynthesis
Ribonucleases - genetics
RNA, Messenger - analysis
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
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Summary:Malignant cell accumulation in B-cell chronic lymphocytic leukemia (B-CLL) is primarily caused by defective apoptosis rather than increased proliferation. To further understand the role of Bcl-2 family members, known regulators of apoptosis, in the abnormal B-CLL survival, we have measured their mRNA levels in fresh B-CLL cells and in cultures undergoing spontaneous apoptosis. Using RNA protection assays we found constitutive expression of most bcl-2 members with high levels of bcl2, bcl-w, bad, bak, bax, and the bcl-2/bax ratio, compared to normal PBL. Spontaneous apoptosis of B-CLL cells by in vitro culture resulted in decreased bcl-2, bcl-w, bfl-1, mcl-1, bak, bax, and bcl-2/bax expression. The pro-apoptotic member bik was only expressed in 5/19 cases and was not modulated during apoptosis, suggesting that bik is not involved in this process. Thus, several Bcl-2 family genes are regulated during B-CLL spontaneous apoptosis and their relative levels may contribute to in vivo progression of the disease.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2004.01.095