title: CD69 is independently prognostic in chronic lymphocytic leukemia: a comprehensive clinical and biological profiling study.
abstract: 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.
  
  
  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.
authors: Department of Hematology, University Tor Vergata, Roma. g.delpoeta@tin.it
authors: Giovanni
authors: G
authors: Del Poeta
authors: Maria Ilaria
authors: MI
authors: Del Principe
authors: Antonella
authors: A
authors: Zucchetto
authors: Fabrizio
authors: F
authors: Luciano
authors: Francesco
authors: F
authors: Buccisano
authors: Francesca Maria
authors: FM
authors: Rossi
authors: Antonio
authors: A
authors: Bruno
authors: Annalisa
authors: A
authors: Biagi
authors: Pietro
authors: P
authors: Bulian
authors: Luca
authors: L
authors: Maurillo
authors: Benedetta
authors: B
authors: Neri
authors: Riccardo
authors: R
authors: Bomben
authors: Cristina
authors: C
authors: Simotti
authors: Angela Maria
authors: AM
authors: Coletta
authors: Michele
authors: M
authors: Dal Bo
authors: Paolo
authors: P
authors: de Fabritiis
authors: Adriano
authors: A
authors: Venditti
authors: Valter
authors: V
authors: Gattei
authors: Sergio
authors: S
authors: Amadori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000069283:Rituximab; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000099192:CD69 Antigens
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D000069283:Rituximab; D014740:Vidarabine; D000099192:CD69 Antigens; C024352:fludarabine