Comparison of CD38, ZAP-70 and P53 markers on Disease Progression and Survival in B- Cell Chronic Lymphocytic Leukemia
Abstract
Chronic lymphocytic leukemia (CLL) is considered the most common B-cell leukemia. Its clinical course is highly variable and depends on clinical, biological and genetic features of leukemic Bcells. Expression of ZAP-70, CD38 and mutated p53 was assessed by flow cytometry methods in 175 BCLL patients and estimated their impact on disease progression rate (DPR) and overall survival (OS). Fifty-one patients (29%) were ZAP-70(+), 81 (46%) were CD38(+), 24 (13.7%) were p53(+). OS was significantly shorter in CD38(+) patients (94.8 vs. 120 months, p<0.001). The similar tendency was found in ZAP-70(+) cases (88 vs.114 months, p<0.01) and in p53(+) patients (88.5 vs. 111.5 months, p=0.48). CD38, ZAP-70 and p53 positive patients have had 4-fold increased mortality rate then the patients with negative markers and this rate was significantly higher after the 6th year of the disease beginning. At multivariable analysis, combined CD38/ZAP-70/p53 status confirmed its independent prognostic role. Double positive CD38/ZAP-70, CD38/p53 and ZAP-70/p53 expressions showed over 19-fold increased DPR above the negative CLL cases (p<0.001). They were classified in a high risk CLL group. The single expressions of these markers were connected with lower DPR and were distributed in middle risk group. CD38, ZAP-70 and p53 negative patients were with the lowest DPR and were classified in the CLL group with good prognosis. ZAP-70 and CD38 expressions appeared to be more predictive than p53 expression and more relevant in defining the cases of B-CLL with higher disease progression rate.
Keywords
Download Options
Introduction
Chronic lymphocytic leukemia (CLL) is considered the most common primary B-cell leukemia. Its clinical course is highly variable and a number of clinical and biological features have been used to separate CLL patients into subgroups with different prognosis and requirement of different therapeutic strategies. Leukemic B-cells may have several characteristics that are related with relatively aggressive disease. These include clinical stage, lymphocyte count and lymphocyte doubling time/ bone marrow infiltration, elevated lactate dehydrogenase (LDH), β2-microglobulin or thymidine kinase, genomic aberrations, gene mutations/deletions (p53, ATM), unmutated variable segments of immunoglobulin heavy chain genes (IgVH), or surrogate markers CD38 and ZAP-70. 1-5
CD38 (also referred to as T10 antigen) expression is not limited only to T- cells but is widely expressed on different hematopoietic and non-hematopoietic cells.6
Conclusion
It can be concluded from this present study that ZAP-70 and CD38 expressions appeared to be more predictive than p53 expression and more relevant in defining the cases of B-CLL with higher disease progression rate.