title: Surface-antigen expression profiling (SEP) in B-cell chronic lymphocytic leukemia (B-CLL): Identification of markers with prognostic relevance.
abstract: Studies of gene expression profiling (GEP) have been successfully used for the identification of molecules to be employed as potential prognosticators. With the aim of identifying the immunophenotypic profile of B-CLL subsets with different prognoses, we investigated by flow cytometry the expression of 36 surface antigens in 117 cases, 113 with survival data. In analogy with GEP, results were analyzed by applying unsupervised hierarchical algorithms (surface-antigen expression profiling, SEP). Distinct immunophenotypic groups (A, B1, B2 and C) were identified, group C (57/117) with longer survivals, as compared to groups A (23/117), B1 (16/117) and B2 (21/117). The immunophenotypic signatures of these groups were characterized by the coordinated and differential over-expression of: i) CD62L, CD54 and CD49c (group C); ii) CD38 and CD49d (group A); iii) none of the above markers (group B1 and B2). Other molecules were either not expressed, widely expressed by all samples, or were variably expressed within the observed B-CLL subgroups, although without a clearly distinguishable pattern. By employing an identical approach for investigating the reactivity of B-cell panel monoclonal antibodies (B-mAbs) in B-CLLs (29 cases) and in 19 B and non-B leukemia/lymphoma cell lines, we found mAbs (B012, B001, B006, B018, B019, B020, B017) mainly unreactive in all the samples, mAbs (B002, B010, B013, B014, B015) strongly reactive in B-CLLs and B-cell lines but not in non-B-cell lines, and mAbs recognizing antigens variably expressed in cell lines and B-CLLs. A hierarchical clustering focused on B-CLLs alone, combining reactivity values for B-mAbs with the expression of CD62L and CD38, these latter antigens identified as leader markers of B-CLL subsets with different prognosis, demonstrated a correlation between CD62L expression and the reactivity of B007, B003, B011 and B005 mAbs. These mAbs may represent potentially novel markers with prognostic relevance in B-CLLs.
authors.affiliation: Clinical and Experimental Hematology Research Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Via Pedemontana Occidentale, 12, Aviano (PN), Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Zucchetto
authors.forename: Paolo
authors.initials: P
authors.lastname: Sonego
authors.forename: Massimo
authors.initials: M
authors.lastname: Degan
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bomben
authors.forename: Michele
authors.initials: M
authors.lastname: Dal Bo
authors.forename: Stefania
authors.initials: S
authors.lastname: Russo
authors.forename: Vincenza
authors.initials: V
authors.lastname: Attadia
authors.forename: Maurizio
authors.initials: M
authors.lastname: Rupolo
authors.forename: Francesco
authors.initials: F
authors.lastname: Buccisano
authors.forename: Agostino
authors.initials: A
authors.lastname: Steffan
authors.forename: Giovanni
authors.initials: G
authors.lastname: Del Poeta
authors.forename: Carlo
authors.initials: C
authors.lastname: Pucillo
authors.forename: Alfonso
authors.initials: A
authors.lastname: Colombatti
authors.forename: Renato
authors.initials: R
authors.lastname: Campanini
authors.forename: Valter
authors.initials: V
authors.lastname: Gattei
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D019041:L-Selectin / Q000032:analysis*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D040081:Protein Array Analysis / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D019041:L-Selectin; D051997:ADP-ribosyl Cyclase 1