The Impact of Selected Apoptotic Markers and Adhesion Molecules on the Treatment Outcome of Chronic Lymphocytic Leukemia

Abstract

We assessed the impact of selected apoptotic markers and adhesion molecules on the treatment outcome. Thirty newly diagnosed patients and 10 healthy subjects were studied. Proapoptotic markers (BCL2, p53, and CD95) and adhesion molecules (CD18, CD54) were assessed by flow cytometry before and after treatment. p21 mRNA was assessed by RT-PCR. Induction was done with the CVP regimen.

Full Abstract

The study included 23 men and 7 women. Median age was 66 years (range, 53-79 years). There were increases of p53 and BCL2 and reductions of CD18 and CD54 in cases compared to control. CD95 did not show significant increase compared to control. There were reductions in BCL2 after (versus before) treatment and increases in CD18 and CD54 after (versus before) treatment. Evaluable patients showed 11 complete remission (CRs; 39.3%), 7 (25%) partial remissions, 6 progressive diseases (21.4%), and 4 stable diseases (14.3%). The observation after treatment was 2 to 13 months. Median time to disease progression (TTP) of the responding patients was 9 months. Death was reported in 1 case. There was an increase in p53 and BCL2 expression in patients who did not achieve CR compared to those with CR and an increase in CD18 level in CR more than no-CR cases. No significant differences were found regarding the expression of CD95 and CD54 between both groups. Comparing the level of expression of the studied markers at initial presentation, there were increases in p53 and decreases in CD18 level in patients with no CR compared to those with CR. There was positive correlation between the expression of p53 and BCL2 and negative correlation between the p53 and CD18 and between BCL2 and CD18. There was significant negative correlation between TTP and BCL2 levels after treatment. Selected cases for p21 mRNA assessment showed negative correlation between p21 mRNA and p53 levels before treatment and decrease in p21 level was associated with poor prognosis and bad response to treatment. In conclusion, measurement of p53 and CD18 level can define a group of patients with aggressive disease who may require more aggressive therapy. BCL2 level after treatment is correlated with TTP.

Acknowledgment

The study was conducted at NCI-Cairo between 2004 and 2007.