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


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.


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.
Servicio General de Citometria, Departamento de Medicina, Centro de Investigacion del Cancer, Universidad de Salamanca, Salamanca, Spain.
Maria Luz
ML
Sanchez
Julia
J
Almeida
Antonio
A
Lopez
Jose Maria
JM
Sayagues
Ana
A
Rasillo
Eugenia A
EA
Sarasquete
Ana
A
Balanzategui
Maria Dolores
MD
Tabernero
Joaquin
J
Diaz-Mediavilla
Carmen
C
Barrachina
Artur
A
Paiva
Marcos
M
Gonzalez
Jesus F
JF
San Miguel
Alberto
A
Orfao
D001483:Base Sequence; D045744:Cell Line, Tumor; D002999:Clone Cells; D003001:Cloning, Molecular / Q000379:methods; D019143:Evolution, Molecular; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008969:Molecular Sequence Data; D010641:Phenotype