Clinical and biological relevance of CD38 expression in chronic lymphocytic leukaemia

In the next part of this study I employed microarray analysis to compare CD38+ and CD38" cells from the same patient purified by high speed cell sorting. CD38+ CLL cells demonstrated a unique gene expression profile when compared to their CD38" counter-parts with 61 genes found to be consistently statistically different. Six genes were investigated further, VEGF, IL-lp, CXCL2, CCR3, ZAP-70 and Akt. Using flow cytometry and Western blotting techniques it was confirmed that these proteins were expressed at significantly higher levels in CD38+ sub-populations when compared to the CD38" sub-populations. CD38+ and CD38" cells from the same patient showed similar drug sensitivity to fludarabine in the majority of samples tested. However, samples from five patients who had received the most prior treatment showed greater resistance to drug therapy in their CD38+ CLL cells. The apoptotic proteins Bcl-2, Bax and Mcl-1 were up-regulated in the CD38+ cells. The combination of CD38 expression data with other prognostic factors such as Vh gene mutational status and ZAP-70 expression will be beneficial in determining the prognosis of the patients and the course of treatment. Also determining the role of CD38 within CLL cells could lead to new therapeutic targets.EThOS - Electronic Theses Online ServiceGBUnited Kingdo