Heterogeneity of neoplastic cells in B-cell chronic lymphoproliferative disorders: biclonality versus intraclonal evolution of a single tumor cell clone

Servicio General de Citometria, Departamento de Medicina, Centro de Investigacion del Cancer, Universidad de Salamanca, Salamanca, Spain.

BACKGROUND AND OBJECTIVES: B-cell chronic lymphoproliferative disorders (B-CLPD) are usually monoclonal expansions of a single B-cell clone. However in some cases, two unrelated B-cell clones co-exist. Additionally, cases with two B-cell subpopulations displaying a similar phenotype but distinct DNA contents exist, the exact nature of these cases remaining unknown. In order to gain insight into the characteristics of these complex B-CLPD we examined two cohorts of patients. MATERIAL AND METHODS: One cohort had two phenotypically distinct B-cell populations (group A; n= 9) and the other, two B-cell subsets showing different DNA contents and/or light scatter properties, but a similar immunophenotype (group B; n= 7). RESULTS: Fluorescent in situ hybridization studies revealed the presence of genetic abnormalities in six cases from group A, either in one (n=5) or the two co-existing B-cell populations (n=1); in all these cases the two B-cell populations showed unrelated IgH gene rearrangements. In all seven cases from group B, the B-cell population showing higher DNA contents had additional chromosomal abnormalities as compared to the other subset; molecular analysis confirmed the monoclonal nature of these cases. INTERPRETATION AND CONCLUSIONS: In summary, we show that in group A, two phenotypically/cytogenetically distinct, unrelated B-cell clones co-exist, while the two B-cell populations from group B appear to represent different stages of evolution of a single clone.