Comparison of Bcl-2, CD38 and ZAP-70 Expression in Chronic Lymphocytic Leukemia

Abstract

Chronic lymphocytic leukemia (CLL) was previously considered a uniform disease characterized by autonomous over-expression of bcl-2. Recently the pathogenic role of bcl-2 has been questioned and attention has turned to prognostic subtypes of CLL differing in CD38 and ZAP-70 expression. However, the relationship between bcl-2 and CD38 or ZAP-70 expression remains uncertain and was investigated using flow cytometric immunophenotyping of 50 CLL specimens. CLL cells were consistently bcl-2 positive but varied in expression level: mean fluorescence intensity (MFI) 45-152. Although there was no significant difference in bcl-2 expression between CD38 or ZAP-70 positive and negative specimens, an inverse correlation was identified between percentage of CD38 positive B-cells and bcl-2 MFI when all (p<0.03, r(2)=0.10) and peripheral blood (p<0.004, r(2)=0.27) samples were analyzed. While bcl-2 levels do not appear to be a major discriminator between indolent and more aggressive subtypes of CLL, CD38 and bcl-2 expression appear to be interrelated.

Keywords: CD38; ZAP-70; bcl-2; chronic lymphocytic leukemia.

Figure 1

Comparison between bcl-2 expression in B-cells and non-B lymphoid cells. B-cells demonstrate significantly higher bcl-2 MFI than non B-lymphoid cells (p<0.0001).

Figure 2

Comparison between bcl-2 MFI and the percentage of CD38 positive B-cells in peripheral blood samples, demonstrating an inverse correlation (p<0.004, r²=0.27).

Figure 3

Flow cytometric dot-plots illustrating bcl-2 expression of 19 positive B-cells and CD19 negative non B-lymphoid cells. (A) Sample with high bcl-2 expression in CLL cells (MFI-R > 1.7). (B) Sample with low bcl-2 expression in CLL cells (MFI-R < 1.7).