The antiapoptotic effects of blood constituents in patients with chronic lymphocytic leukemia

Abstract

B-CLL cells exhibit decreased spontaneous apoptosis, which is partially prevented by humoral (AS) and cellular (T cells and B-CLL cells) factors. The equilibrium between apoptotic and antiapoptotic factors changes with disease progression.

Good prognosis cytogenetics in B-cell chronic lymphocytic leukemia is associated in vitro with low susceptibility to apoptosis and enhanced immunogenicity

“…In contrast, spontaneous apoptosis occurs rapidly in most, but not all, B-CLL samples that are cultured in vitro. Survival of cells in vivo and apoptosis in vitro have been attributed to a variety of external humoral [27][28][29][30][31][32] If spontaneous apoptosis of B-CLL cells plays an important role in determining disease progression, and in vitro apoptosis corresponds to in vivo cell death, we would expect a lower rate of spontaneous apoptosis, and more viable cells, in samples with poor prognosis cytogenetics. On the other hand, it is known that a high level of serum LDH, which is a measure of tumor burden and turnover, is associated with rapid disease progression and worse clinical prognosis in B-CLL.…”

Soluble CD14 is a novel monocyte-derived survival factor for chronic lymphocytic leukemia cells, which is induced by CLL cells in vitro and present at abnormally high levels in vivo

“…This is in accordance with results shown by Bomstein et al, demonstrating that apoptotic levels of isolated CLL cells in culture can be decreased by cultivating them at high cell density (1 ϫ 10 6 cells/mL). 28 Extensive DNA microarray and cytokine antibody array data using survival-inducing CLL cultures identified a variety of inflammatory cytokines and signaling pathways, which showed up-regulated expression and increased secretion or activation. Because many of those cytokines are known to be specific for monocytes and macrophages, we hypothesized that blood-derived monocytes might be the source of the observed survival-inducing activity.…”

Highly purified CD38+ and CD38− sub-clones derived from the same chronic lymphocytic leukemia patient have distinct gene expression signatures despite their monoclonal origin

“…In these experiments, we used autologous serum because it has been shown to minimize spontaneous apoptosis. 27 The CD38 þ subclones showed a consistently lower level of spontaneous apoptosis when compared with the CD38 À sub-clones and the mixed cultures at all the time points tested (Figure 3a). The purified CD38 À CLL cells showed the highest percentage apoptosis and the mixed cultures were less viable than the CD38 þ sub-clones, but more viable than the CD38 À Differential protein expression of VEGF and IL-1b in CD38 þ and CD38 À sub-clones.…”