CD69 is independently prognostic in chronic lymphocytic leukemia: a comprehensive clinical and biological profiling study

Background CD69 is expressed in several hemopoietic cells and is an early activation marker in chronic lymphocytic leukemia. Chronic lymphocytic leukemia is a clinically heterogeneous disease which needs novel prognostic parameters which can be easily and efficiently managed. Design and Methods We investigated CD69 by flow cytometry in a series of 417 patients affected by chronic lymphocytic leukemia and compared this to other biological and clinical prognosticators. Results CD69 was associated with Rai stages ( P =0.00002), β2-microglobulin ( P =0.0005) and soluble CD23 ( P <0.0001). CD69 and ZAP-70 ( P =0.018) or CD38 ( P =0.00015) or immunoglobulin variable heavy chain gene mutations ( P =0.0005) were also significantly correlated. Clinically, CD69 positive chronic lymphocytic leukemias received chemotherapy more frequently (74%; P <0.0001), and presented a shorter duration of response after fludarabine plus rituximab ( P =0.010) as well as shorter progression free survival and overall survival ( P <0.0001). CD69 demonstrated true additive prognostic properties, since the CD69+ plus ZAP-70+ or CD38+ or immunoglobulin variable heavy chain gene unmutated patients had the worst progression free survival and overall survival ( P <0.0001). Interestingly, low CD69 expression was necessary to correctly prognosticate the longer progression free survival of patients with a low tumor burden of β2-microglobulin ( P =0.002), of soluble CD23 ( P =0.020), or of Rai stages 0-I ( P =0.005). CD69 was confirmed to be an independent prognostic factor in multivariate analysis of progression free survival ( P =0.017) and overall survival ( P =0.039). Conclusions Our data indicate that CD69 is significantly correlated with poor clinical and biological prognostic factors and is confirmed to be an independent disease prognosticator. This supports its introduction in a routine laboratory assessment and, possibly, in a prognostic scoring system for chronic lymphocytic leukemia, after an adequate standardization process.