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 pr ogression may thus come from a constitutive but altered expression of a number of genes that results in extended B-CLL cells life span, incr eased proliferative capacity and diminished cell death. B-CLL cells ex press a number of surface markers that characterise the normal B-cells phenotype. However, B-CLL cells are CD5 positive and most of them als o express CD6, surface receptors that are present in just a small subs et of normal B-cells. When exploring CD6 function, we found out that c ross-linking of CD6 protected B-CLL from anti-IgM-induced apoptosis. C D6 activation blocked anti-IgM-induced Bar, up-regulation and, by doin g so, corrected an imbalance in the Bcl-2/Bax ratio that accompanies a poptosis. Here, we review all surface receptors and cytokines that hav e been described as participating in the induction or protection of B- CLL apoptosis together with data on chemosensitivity and gene modulati on, data on the Fas receptor/Fas ligand system, and the implications o f all the latter for B-CLL cell survival.