Activation by CD40 Ligand Shifts Bcl-2 Family Protein Expression from Death-by-Default to Survival-by-Default (original) (raw)

Blood

Abstract

CLL cells survive and accumulate in vivo and yet leukaemic cells isolated from the peripheral blood rapidly die. We have used mouse fibroblast L-cells transfected with CD40 ligand (CD40L) in combination with IL-4 to reproduce some features of the in vivo microenvironment, which is essential for CLL cell proliferation. As anticipated we found that leukaemic cells survive and proliferate in this system. Also CD23 expression increases, but unexpectedly CD38 expression increased to varying degrees in all patients and CD5 expression decreased. Changes in CD23 and CD38 have been reported in CLL cells in lymph nodes and support the concept that we are able to some extent reproduce the in vivo microenvironment. Next we carried out a systematic analysis of Bcl-2 family proteins by Western Blot analysis. On tissue culture plastic and non-transfected L-cells Bcl-2 is the predominant pro-survival protein. The activator BH3-only protein Bim is expressed together with the sensitiser BH3-only Puma...

Simon Wagner hasn't uploaded this paper.

Let Simon know you want this paper to be uploaded.

Ask for this paper to be uploaded.