Evaluation of CD69 expression as a prognosticator in chronic lymphocytic leukemia

Introduction Chronic lymphocytic leukemia (CLL) is themost common type of adult leukemia in the western world.It is a malignancy of mature B cells involving the blood,bone marrow (BM), and lymphoid tissues, and its cellsarise from polyclonal expansion of CD5+ B lymphocytestransformed into a monoclonal population by mutationalagents. CD69 is an integral membrane protein belongingto the lectin family. It is expressed after activation in allBM-derived cells except erythrocytes. CLL exhibits featuresof activated and antigen-experienced B lymphocytes andCD69 overexpression. CD69 is significantly correlated withpoor clinical and biological prognostic factors, and thissupports its introduction into routine laboratory assessmentand, possibly, in a prognostic scoring system for CLL afteran adequate standardization process.Objective The aim of this study was to detect CD69expression in newly diagnosed patients with CLL by flowcytometry and correlate it with clinical and laboratoryparameters to evaluate it as a prognostic factor.Patients and methods This study was conducted on40 B-CLL patients who attended Ain Shams UniversityHospitals over 1 year. All patients were subjected to fullmedical history and clinical examination, RAI stagingaccording to disease burden and the degree of BMinvolvement, abdominal ultrasonography, completeblood count with examination of peripheral blood smears,BM aspiration with morphological examination, andimmunophenotyping of BM or whole peripheral bloodapplying monoclonal antibodies CD20, CD79b, FMC7,serum IgM, CD5/CD19, CD10, CD103, CD123, CD23, andCD38, and κ and λ light chains and CD69 expression.Results In the current study all of the studied B-CLLpatients expressed CD69. Among the 40 studied patients23 had high CD69 expression (group I) and 17 had lowCD69 expression (group II). A highly significant elevationin group I patients compared with group II patientswas found (P = 0.000). A highly significant reduction inhemoglobin (Hb) level (P = 0.001), elevation in lactatedehydrogenase concentration (P = 0.006), elevation inRAI staging, and elevation in CD38 expression (P = 0.005)were observed in group I. A highly significant negativecorrelation was found between CD69% and Hb level (P =0.008) and platelet count (P = 0.009). A highly significantpositive correlation was found between CD69% andhepatomegaly (P = 0.008) and RAI stage (P = 0.008) andsignificant positive correlation was found between CD69%and CD38% expression (P = 0.012). An association studywas conducted between CD69% expression and all thestandard prognostic factors in B-CLL patients. Therewas a highly significant association between CD69%expression and presence of hepatomegaly (P = 0.002)and a significant association between CD69% expressionand presence of splenomegaly (P = 0.028) and low Hblevels (P = 0.013).Conclusion Several clinical and biological variables havebeen reported to predict the outcome of CLL patients,such as advanced patient age, male sex, higher absolute lymphocyte count, greater extent of lymphadenopathy, and raised serum β2-microglobulin levels, all of which are associated with inferior prognosis. In the current study all of the studied B-CLL patients expressed CD69. CLL patients were divided into two subsets with significantly different prognosis: those with high CD69 (group I) (≥30%) and those with low CD69 (group II) ( 30%) expression; both were compared with respect to the different studied parameters. There was highly significant elevation of CD69 in group I compared with group II. There was a highly significant reduction in Hb level and elevation in lactate dehydrogenase concentration in group I patients in comparison with group II patients. A highly significant relation was found between the two groups with respect to RAI staging: an advanced RAI stage was found among group I patients in comparison with group II patients. The current study evaluated CD69 as a prognosticator and studied the significant association of its high expression with the standard prognostic factors, notably splenomegaly (P = 0.028) and hepatomegaly (P = 0.002), low Hb level, low platelet count, and advanced RAI stage. CD69 expression is associated with both immunoglobulin variable heavy chain mutation status and survival. It is recommended to perform a larger prospective study on CD69 expression in B-CLL patients, studying its relation to overall survival and progression-free survival and its re-evaluation during the course of treatment as we recommend assessment of this marker by flow cytometry among independent prognostic markers in B-CLL.