B-cell monoclonal lymphocytosis and B-cell abnormalities in the setting of familial B-cell chronic lymphocytic leukemia.
BACKGROUND
Among all hematologic malignancies, B-cell chronic lymphocytic leukemia (BCLL) has the highest familial clustering (three- to sevenfold increase), strongly suggesting a genetic component to its etiology. Familial BCLL can be used as a model to study the early pathogenesis of this disease.


METHODS
We examined nine kindreds from the National Cancer Institute's Familial BCLL Registry, consisting of 19 affected members with BCLL and 33 clinically unaffected first-degree relatives. Flow cytometric immunophenotyping to detect a B-cell monoclonal lymphocytosis (BCML) was performed. Monoclonality was confirmed by polymerase chain reaction analysis of whole blood DNA. Cell cycle analysis for aneuploidy was conducted.


RESULTS
In all affected individuals, we observed the classic BCLL CD5/CD19/CD20/CD23 immunophenotypic patterns. Six of the 33 unaffected individuals (18%) had evidence of BCML. Additional individuals (13/33, 39%) showed some other abnormality, whereas 14 individuals (42%) were normal. Based on an estimated prevalence of 0.7% for BCML in the general population, the finding of six subjects (18%) with clonal abnormalities in this relatively modest sample was significantly greater than expected (i.e., 18% vs. 0.7%, P < 5.7 x 10(-9)).


CONCLUSIONS
Individual components of BCML and other B-cell abnormalities were observed in almost half of the apparently unaffected individuals. Our findings suggested that BCML may be an early detectable abnormality in BCLL. The spectrum of some of these observed abnormalities suggested the involvement of different B-cell subpopulations or different pathways in clonal evolution. Population-based, longitudinal studies will be required to determine the incidence of BCML and other B-cell abnormalities and their relation to disease progression in BCLL and other closely related B-cell lymphoproliferative disorders.
Marti
Gerald E
GE
Flow and Image Cytometry Section, Laboratory Stem Cell Biology, Division of Cell and Gene Therapies, Center for Biologics Research and Evaluation, Food and Drug Administration, Bethesda, Maryland20892, USA. gemarti@helix.nih.gov
Carter
Patricia
P
Abbasi
Fatima
F
Washington
Glennelle C
GC
Jain
Nisha
N
Zenger
Vincent E
VE
Ishibe
Naoko
N
Goldin
Lynn
L
Fontaine
Laura
L
Weissman
Nancy
N
Sgambati
Maria
M
Fauget
Guy
G
Bertin
Pablo
P
Vogt
Robert F
RF
Slade
Barbara
B
Noguchi
Philip D
PD
Stetler-Stevenson
M A
MA
Caporaso
Neil
N
D001402:B-Lymphocytes / Q000473:pathology*; D002453:Cell Cycle / Q000276:immunology; D002999:Clone Cells; D005260:Female; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D016130:Immunophenotyping; D015994:Incidence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D008218:Lymphocytosis / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D008297:Male; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012307:Risk Factors