Definition of progression risk based on combinations of cellular and molecular markers in patients with Binet stage A chronic lymphocytic leukaemia.
IGHV mutational status and ZAP-70 or CD38 expression correlate with clinical course in B-cell chronic lymphocytic leukaemia (CLL). The three markers may be discordant in the single case and there is no consensus on their combined use in clinical practise. This multicenter study investigated this issue. Two-hundred and sixty-two Binet stage A patients were studied for the three markers. Sixty patients were profiled with HG-U133A gene expression chips. Disease progression was determined by time from diagnosis to treatment (TTT). The probability of being treatment-free at 3 years was significantly shorter in patients with unmutated IGHV genes (IGHVunmut 66% vs. 93%, chi square of log-rank = 30, P < 0.0001), ZAP-70 positive (ZAP-70pos 73% vs. 96%, chi square of log-rank = 8.2, P = 0.004) or CD38-positive cells (CD38pos 68% vs. 91%, chi square of log-rank = 21, P < 0.0001). Cox multivariate regression analysis showed that the three markers had an independent predictive value for TTT of similar power. A prognostic system based on presence of none (low-risk), one (intermediate-risk) or two or three (high-risk) markers was generated. Based on such criteria, 56%, 23% and 21% of cases were clustered in low (HR = 1), intermediate [HR = 2.8, 95% confidence interval (CI) 2.4-5.8] and high-risk group (HR = 8.0, 95% CI 3.9-16.2). Specific transcriptional patterns were significantly associated with risk groups.
Morabito
Fortunato
F
Unità Operativa Complessa di Ematologia, Azienda Ospedaliera, Cosenza, Italy. fortunato_morabito@tin.it
Cutrona
Giovanna
G
Gentile
Massimo
M
Matis
Serena
S
Todoerti
Katia
K
Colombo
Monica
M
Sonaglio
Claudia
C
Fabris
Sonia
S
Reverberi
Daniele
D
Megna
Mauro
M
Spriano
Mauro
M
Lucia
Eugenio
E
Rossi
Edoardo
E
Callea
Vincenzo
V
Mazzone
Carla
C
Festini
Gianluca
G
Zupo
Simonetta
S
Molica
Stefano
S
Neri
Antonino
A
Ferrarini
Manlio
M
D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D050438:Genes, Immunoglobulin Heavy Chain; D005819:Genetic Markers; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008297:Male; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D018570:Risk Assessment / Q000379:methods; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000032:analysis
D014408:Biomarkers, Tumor; D005819:Genetic Markers; D007135:Immunoglobulin Variable Region; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D051997:ADP-ribosyl Cyclase 1