الفهرس 
Chronic Lymphocytic Leukemia (CLL)Only 14 pages are availabe for public view
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Abstract
Chronic lymphocytic leukemia (CLL) is the most frequent type of leukemia and affects mainly elderly individuals. CLL follows an extremely variable clinical course with overall survival times ranging from months to decades.
The staging systems developed by Rai et al, (1975) and Binet et al, (1981) are standard methods of assessing prognosis in chronic lymphocytic leukemia (CLL). However, since these systems cannot identify stable or progressive forms of the disease, there has been a continual effort to identify other prognostic factors in CLL.
Over the last few years, technological advances have led to identification of important biological and genetic parameters related to the clinical course of B-CLL. The immunoglobulin variable heavy chain (IgVH) gene was determined as one of the most powerful prognostic factors, where B-CLL cases with unmutated IgVH genes are characterized by an unfavorable clinical outcome. In contrast to the technically demanding and expensive method of IgVH mutations analysis, ZAP-70 can be conveniently measured using the flow cytometry. ZAP-70, a 70 KD zeta-chain CD3- receptor – associated protein tyrosine kinase (PTK) of T lymphocytes. ZAP-70, a member of the SYK-ZAP-70 protein, is normally expressed in T cells and natural killer cells and has a critical role in the initiation of T-cell signaling. The ZAP-70 (zeta-associated protein) was shown to be the most promising surrogate marker for IgVH mutation status, with a high predictive value.
The present study aimed to evaluate the prognostic impact of ZAP-70 expression, and its association with disease progression, and correlate the level of ZAP-70 expression with the expression of other cell markers, particularly those with known prognostic significance.
The current study was carried out on 30 CLL patients and 20 hematologicaly and biochemicaly normal volunteers as control group.
All patients were subjected to complete history, thorough clinical examination and laboratory investigations including: complete blood count, routine biochemical profile, bone marrow aspiration with examination of Leishman-stained peripheral blood and bone marrow smears, immunophenotyping, flowcytometric determination of total ZAP-70 expression, expression of ZAP-70 by different lymphocytes subpopulations (B, T & NK lymphocytes) and co-expression of ZAP-70 with CD38 and ZAP-70 with FMC7.
In this study, the highest level of ZAP-70 expression, in CLL patients was detected among B cells, followed by T and NK cells. While in the control group, the highest level was among T cells followed by NK and lowest expression by B cells. The level of ZAP-70 was higher among patients’ group when compared to control group.
Among the ZAP-70 positive group of patients; with ≥ 20% of lymphocytes expressing ZAP-70, there were shorter LDT, higher incidence of Lymphadenopathy, higher % of patients presented with Binet stage C, higher percentage of patients showing poor response to treatment, as compared to the ZAP-70 negative group of patient.
The level of CD38 expression was determined in 30 CLL cases, a significant difference between the CD38 positive and negative group of patients, was not found as regards the response to treatment.
The patients exhibiting positive ZAP-70+ve/CD38+ve (concordant positive) and patients with ZAP-70-ve/CD38-ve (concordant negative) were compared to understand the usefulness of analyzing both of these prognostic markers together. The concordant positive group had poorer response to treatment, and higher incidence of lymphadenopathy compared to patients with concordant negative expression. Moreover, there was a positive correlation between ZAP-70 expression and the dual coexpression of ZAP-70/CD38 among the CLL patients, which strengthen the relationship between both markers.
Finally, we were able to characterize that patients with positive total ZAP-70 expression, had a poorer response to treatment and high tumor load presentation. These findings implied that ZAP-70 positive expression conferred a poor prognosis.