ZAP-70, IgVh, and cytogenetics for assessing prognosis in chronic lymphocytic leukemia.
BACKGROUND
New prognostic factors such as IgVh mutational status, ZAP-70 protein expression and cytogenetic abnormalities have shown to offer important prognostic information for patients with chronic lymphocytic leukemia (CLL). Our aim was to evaluate the optimal cut-off for IgVh mutational status, ZAP-70 expression and cytogenetic abnormalities in association with disease progression defined as the need for treatment within 3~years from diagnosis in 170 patients with B-CLL.


METHODS
Receiver operating characteristics (ROC) analysis and multivariate general linear models (GLMs) were used to investigate the most significant cut-off values of these biomarkers and their prognostic impact.


RESULTS
Our findings estimated that the optimal cut-off for IgVh mutation status and for ZAP-70 protein expression was 97% and 16.5% respectively and a high concordance between the two was demonstrated. We identified 30% as being the best-cut-off for 17p-, 11q- and 6q-. In univariate analysis 17p- was found to be a significant predictor of the event only for the whole population. Multivariate analysis including all biological parameters, identified 11q deletion as the only significant regressor.


CONCLUSIONS
We assessed that IgVh mutational status, ZAP-70 protein and 6q- are powerful prognostic markers. Analyses of all these factors revealed that 11q deletion was the strongest predictor of disease progression in B-CLL.
Trojani
Alessandra
A
Niguarda Cà Granda Hospital, Division of Hematology, Milan, Italy. alessandra.trojani@ospedaleniguarda.it
Montillo
Marco
M
Nichelatti
Michele
M
Tedeschi
Alessandra
A
Colombo
Chiara
C
Veronese
Silvio
S
Mura
Maria Angela
MA
Ricci
Francesca
F
Scarpati
Barbara
B
Colosimo
Anna
A
Lodola
Milena
M
Morra
Enrica
E
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis*; D002469:Cell Separation; D003582:Cytogenetics / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D017353:Gene Deletion; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D012372:ROC Curve; D012680:Sensitivity and Specificity; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human