Intrinsic apoptosis defects underlie to a large extent the extended survival of malignant B
cells in chronic lymphocytic leukemia (CLL). Here, we show that the Shc family adapter
p66Shc uncouples the B-cell receptor (BCR) from the Erk-and Akt-dependent survival
pathways, thereby enhancing B-cell apoptosis. p66Shc expression was found to be
profoundly impaired in CLL B cells compared with normal peripheral B cells. Moreover,
significant differences in p66Shc expression were observed in patients with favorable or …

Abstract 801 Intrinsic defects in the apoptotic circuitry underlie to a large extent the extended
survival of malignant B cells in chronic lymphocytic leukemia (CLL) and are moreover
believed to be responsible for their resistance to chemotherapy. We have recently
demonstrated that p66Shc, a member of Shc family of protein adapters, acts as a promoter of
apoptosis in T cells. Here we show that p66Shc uncouples the B-cell antigen receptor (BCR)
from the Erk and Akt dependent survival pathways, thereby enhancing B-cell apoptosis …