Background. Biologic risk factors such as immunoglobulin variable heavy chain (IgVH) gene mutation status and CD38 and ZAP-70 expression levels, along with genomic aberrations, have been identified in B-CLL and their prognostic impact has been intensively evaluated in the disease. Aims. We investigated the incidence of the known major cytogenetic alterations (+12 and 13q14, 17p13, 11q23 deletions) in Binet A B-CLL patients included in the prospective multicenter O-CLL1 GISL trial. The study was performed by FISH in 319 out of 377 patients enrolled to date. Methods. Molecular markers characterization and FISH analyses were previously reported (Cutrona et al. Haematologica, 2008; Fabris et al. GCC, 2008). Results. At least one abnormality was found in 209/319 (65.5%) cases. The most frequent abnormality was del(13)(q14), which was detected in 160 cases (50%) followed by +12 (42/319, 13 2%) (one case harboring 17p13 deletion), del(17)(p13) (8/319, 2.5%) and del(11)(q23) (18/319, 5.6%). 13q14 deletion was found as a sole abnormality in 142 (44.5%) patients; in the remaining cases, it was combined with +12 (3 pts) and 17p13 (4 pts) or 11q23 deletions (11 pts). The 13q deletion was found as a monoallelic deletion in 127/160 (79.3%); in the remaining 33 cases the presence of a biallelic deletion was found in >20% of interphase nuclei. No acquisition of new cytogenetic aberrations was evidenced among the 13 patients developing progressive disease (range, 6 to32 months; median, 20 months). In only one case, the proportion of nuclei with 17p13 and 13q14 deletions increased from the time of diagnosis (from 33% to 92%). Biomarkers data were available in all of the patients. CD38 percentages (mean value±sem) were 9.3±1.5, 16.2±2.0, 53.4±5.4, 23.3±1.1,47.3±13.6, 35.1±10.3 for del(13)(q14), normal karyotype, +12, del(11)(q23), del(17)(p13) and multiple alterations, respectively (P<0.0001). The percentages of IgVH mutations significantly correlated with cytogenetic alterations; namely, 5.5±0.3 for cases with del(13)(q14), 4.6±0.4 for normal karyotype, 2.6±0.5 for +12, 0.3±0.2 for del(11)(q23), 1.9±1.1 for del(17)(p13) and 1.2±0.6 for multiple alterations (P<0.0001). Similarly, a significant correlation was found for ZAP-70 expression: namely 33.5±1.8 for cases with del(13)(q14), 38.6±2.2 for normal karyotype, 47.5±3.5 for +12, 71.4±8.2 for del(11)(q22), 38.3±12.5 for del(17)(p13) and 46.0±6.1 multiple alterations (P<0.0001). Finally, cytogenetic abnormalities were clustered in 3 risk groups [i.e. low del(13)(q14) and normal; intermediate (+12); and high risk del(11)(q23) and del(17)(p13)] and correlated with a scoring system in which patients were stratified in 4 different groups according to the absence (group 0) or presence of 1 (group 1), 2 (group 2) or 3 (group 3) biomarkers (Morabito et al., BJH, 2009,). Notably, 154/162 cases scoring 0, gathered in the low FISH group, whereas 16/20 high FISH risk cases clustered in scoring 2-3 (P<0.0001). Conclusions. Our data indicate that cytogenetic abnormalities predicting unfavorable prognosis show a relatively low incidence in newly diagnosed Binet stage A B-CLL patients and are significantly associated with negative prognostic biomarkers predictive of disease progression. Furthermore, preliminary results in a limited number of cases indicate that the acquisition of new abnormalities seem to be an infrequent event during disease progression.
INCIDENCE OF CYTOGENETIC ABNORMALITIES IN NEWLY DIAGNOSED BINET STAGE A B-CLL AND RELATIONSHIP WITH PROGNOSTIC BIO-MARKERS: UPDATED RESULTS ON 319 PATIENTS INCLUDED IN THE PROSPECTIVE O-CLL1 GISL STUDY / S., Fabris; G., Cutrona; M., Gentile; S., Matis; E., Pesce; F., Di Raimondo; C., Musolino; M., Gobbi; N., Di Renzo; F., Mauro; R., Cantaffa; M., Brugiatelli; F., Merli; S., Zupo; C., Mammi; L., Baldini; F., Angrilli; G., Quintana; U., Consoli; G., Bertoldero; E., Iannitto; P., Di Tonno; A., Fragasso; S., Molica; P., Musto; Mc, Cox; G., Festini; V., Callea; Sacchi, Stefano; A., Cortelezzi; G., Lambertenghi Deliliers; R., Foà; Federico, Massimo; F., Morabito; M., Ferrarini; A., Neri. - In: HAEMATOLOGICA. - ISSN 0390-6078. - ELETTRONICO. - 95:(2010), pp. 37-38. (Intervento presentato al convegno nd tenutosi a Barcelona nel June 10-13, 2010).