A scoring system based on the expression of six surface molecules allows the identification of three prognostic risk groups in B-cell chronic lymphocytic leukemia.
We have previously identified 12 surface antigens whose differential expression represented the signature of B-cell chronic lymphocytic leukemia (B-CLL) subsets with different prognosis. In the present study, expression data for these antigens, as determined in 137 B-CLL cases, all with survivals, were utilized to devise a comprehensive immunophenotypic scoring system of prognostic relevance for B-CLL patients. In particular, univariate z score was employed to identify the markers with greater prognostic impact, while maximally selected log-rank statistics were chosen to define the optimal cut-off points capable to split patients into two groups with different survivals. A weighted immunophenotypic scoring system was developed by integrating results from these analyses. Six antigens were selected: three positive prognosticators (CD62L, CD54, CD49c) and three negative prognosticators (CD49d, CD38, CD79b), with cut-off values ranging from 30% to 50% of positive cells. By weighing the expression of each marker according to its statistical power, a complete scoring system, with point values comprised between 0 (complete absence of phenotypic conditions associated with good prognosis) and 9 (all the phenotypic conditions associated with good prognosis fulfilled), allowed to split the whole set of B-CLL patients, into three distinctive prognostic groups (P = 4.78 x 10(-11)) with high- (score 0-3), intermediate- (score 4-6), and low- (score 7-9) risk of death. The three risk groups showed different distribution of cases as for Rai's stages, IgVH mutations, and ZAP-70 expression. The proposed immunophenotypic scoring system may be an additional useful tool in routine diagnostic/prognostic procedures for B-CLL.
Zucchetto
Antonella
A
Clinical and Experimental Hematology Research Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy.
Bomben
Riccardo
R
Dal Bo
Michele
M
Sonego
Paolo
P
Nanni
Paola
P
Rupolo
Maurizio
M
Bulian
Pietro
P
Dal Maso
Luigino
L
Del Poeta
Giovanni
G
Del Principe
Maria Ilaria
MI
Degan
Massimo
M
Gattei
Valter
V
D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis*; D018941:Antigens, CD19 / Q000032:analysis; D051925:CD79 Antigens / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping / Q000706:statistics & numerical data; D039422:Integrin alpha3 / Q000032:analysis; D039441:Integrin alpha4 / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D019041:L-Selectin / Q000032:analysis; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis
D015703:Antigens, CD; D018941:Antigens, CD19; D051925:CD79 Antigens; D039422:Integrin alpha3; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D039441:Integrin alpha4; D051997:ADP-ribosyl Cyclase 1