Regulation of B-CLL apoptosis through membrane receptors and Bcl-2 family proteins.
The accumulation of monoclonal chronic lymphocytic leukemia B (B-CLL) cells may be due to excessive proliferation and longevity. Clinical progression may thus come from a constitutive but altered expression of a number of genes that results in extended B-CLL cells life span, increased proliferative capacity and diminished cell death. B-CLL cells express a number of surface markers that characterise the normal B-cells phenotype. However, B-CLL cells are CD5 positive and most of them also express CD6, surface receptors that are present in just a small subset of normal B-cells. When exploring CD6 function, we found out that cross-linking of CD6 protected B-CLL from anti-IgM-induced apoptosis. CD6 activation blocked anti-IgM- induced Bax(alpha) up-regulation and, by doing so, corrected an imbalance in the Bcl-2/Bax ratio that accompanies apoptosis. Here, we review all surface receptors and cytokines that have been described as participating in the induction or protection of B-CLL apoptosis together with data on chemosensitivity and gene modulation, data on the Fas receptor/Fas ligand system, and the implications of all the latter for B-CLL cell survival.
Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.
L M
LM
Osorio
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M
Jondal
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M
Aguilar-Santelises
D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology
D016207:Cytokines; D019253:Proto-Oncogene Proteins c-bcl-2; D011956:Receptors, Cell Surface; D019014:fas Receptor