Signature of B-CLL with different prognosis by Shrunken centroids of surface antigen expression profiling.
With the aim of identifying the immunophenotypic profile of B-cell chronic lymphocytic leukemia (B-CLL) subsets with different prognosis, we investigated by flow cytometry the expression of 36 surface antigens in 123 cases, all with survivals. By analyzing results with unsupervised (hierarchical and K-means clustering) algorithms, three distinct immunophenotypic groups (I, II, and III) were identified, group I (51/123) with longer survivals, as compared to the group II (36/123) and III (36/123). The immunophenotypic signatures of these groups, as determined by applying the nearest Shrunken centroids method as class predictor, were characterized by the coordinated and differential expression of 12 surface markers, that is, group I: above-average expression of CD62L, CD54, CD49c, and CD25, below-average expression of CD38; group II: above-average expression of CD38, CD49d, CD29, and CD49e; and group III: below-average expression of the above markers, overexpression of CD23, CD20, SmIg, and CD79b. As opposed to groups II-III, group I B-CLLs lacked expression of ZAP-70 and activation-induced cytidine deaminase in the majority of cases, while more frequently had mutated IgV(H) genes and IgV(H) mutations consistent with antigen-driven selection. Our findings contribute to improve the immunophenotypical identification of disease subsets with different prognosis and suggest a set of surface antigens to be employed as prognosticators in routine diagnostic/prognostic procedures.
Zucchetto
Antonella
A
Clinical and Experimental Hematology Research Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy.
Sonego
Paolo
P
Degan
Massimo
M
Bomben
Riccardo
R
Dal Bo
Michele
M
Russo
Stefania
S
Attadia
Vincenza
V
Rupolo
Maurizio
M
Buccisano
Francesco
F
Del Principe
Maria Ilaria
MI
Del Poeta
Giovanni
G
Pucillo
Carlo
C
Colombatti
Alfonso
A
Campanini
Renato
R
Gattei
Valter
V
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D016000:Cluster Analysis; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D016019:Survival Analysis; D051746:ZAP-70 Protein-Tyrosine Kinase; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D007135:Immunoglobulin Variable Region; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D043525:Cytosine Deaminase; D003564:Cytidine Deaminase