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Published on: July 20, 2016
CD69 is independently prognostic in chronic lymphocytic leukemia: a comprehensive clinical and biological profiling
Giovanni Del Poeta1, Maria Ilaria Del Principe, Antonella Zucchetto
1Department of Hematology, University Tor Vergata, Roma. g.delpoeta@tin.it
Insights
CD69 is a novel prognostic marker for chronic lymphocytic leukemia (CLL). High CD69 expression correlates with poor prognosis and can be integrated into routine assessments for better patient management.
Area of Science:
- Hematology
- Oncology
- Immunology
Background:
- Chronic lymphocytic leukemia (CLL) is a heterogeneous hematologic malignancy.
- Novel prognostic markers are needed for effective patient management.
- CD69 is an early activation marker expressed on hemopoietic cells.
Purpose of the Study:
- To investigate the prognostic value of CD69 in chronic lymphocytic leukemia (CLL).
- To compare CD69 with established clinical and biological prognosticators.
- To assess CD69 as an independent prognostic factor in CLL.
Main Methods:
- Flow cytometry analysis of CD69 expression in 417 CLL patients.
- Correlation analysis with clinical parameters (Rai stages) and biological markers (β(2)-microglobulin, soluble CD23, ZAP-70, CD38, IgHV gene mutations).
- Multivariate analysis to determine independent prognostic value.
Main Results:
- CD69 expression significantly correlated with adverse prognostic factors including Rai stages, β(2)-microglobulin, soluble CD23, ZAP-70, CD38, and unmutated IgHV genes.
- CD69 positivity was associated with increased chemotherapy use, shorter response duration to fludarabine plus rituximab, and reduced progression-free and overall survival.
- CD69 demonstrated additive prognostic value when combined with other markers and was an independent predictor of survival.
Conclusions:
- CD69 is a significant prognosticator in chronic lymphocytic leukemia (CLL), correlating with poor clinical and biological outcomes.
- CD69 is an independent prognostic factor for progression-free and overall survival in CLL.
- Introduction of CD69 into routine laboratory assessments and prognostic scoring systems for CLL is recommended, pending standardization.
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), β(2)-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 β(2)-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.
