Prevalence and frequency of circulating t(14;18)-MBR translocation carrying cells in healthy individuals.
The t(14;18) translocation is a common genetic aberration that can be seen as an early step in pathogenesis of follicular lymphoma (FL). The significance of low level circulating t(14;18)-positive cells in healthy individuals as clonal lymphoma precursors or indicators of risk is still unclear. We determined the age dependent prevalence and frequency of BCL2/IgH rearrangements in 715 healthy individuals ranging from newborns to octo- and nonagenarians. These results were compared with number of circulating t(14;18)-positive cells in 108 FL patients at initial presentation. The overall prevalence of BCL2/IgH junctions in this large sample was 46% (327/715). However, there was a striking dependence upon age. Specifically, among individuals up to 10 years old, none had detectable circulating t(14;18)-positive cells. In the age groups representing 10-50 years old, we found a steady elevation in the prevalence of BCL2/IgH junctions up to a prevalence of 66%. Further increases of the prevalence in individuals older than 50 years were not seen. The mean frequency of BCL2/IgH junctions in healthy individuals > or =40 years (18-26 x 10(-6)) was significantly higher than in younger subjects (7-9 x 10(-6)). Four percent (31/715) of individuals carried more than one t(14;18)-positive cell per 25,000 peripheral blood mononuclear cells (PBMNCs). In comparison, 108 stage III/IV FL patients had a median number of circulating t(14;18)-positive malignant FL cells of about 9200/1 million PBMNCs (range 7-1,000,000). These findings will further improve the understanding of the relevance of t(14;18)-positive cells in healthy individuals as a risk marker toward the development into lymphoma precursors.
Schüler
Frank
F
Department of Hematology and Oncology, Ernst-Moritz-Arndt-University Greifswald, Sauerbruchstrasse, Greifswald, Germany.
Dölken
Lars
L
Hirt
Carsten
C
Kiefer
Thomas
T
Berg
Tobias
T
Fusch
Gerhard
G
Weitmann
K
K
Hoffmann
W
W
Fusch
Christoph
C
Janz
Siegfried
S
Rabkin
Charles S
CS
Dölken
Gottfried
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002648:Child; D002675:Child, Preschool; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008224:Lymphoma, Follicular / Q000235:genetics; D008875:Middle Aged; D015995:Prevalence; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic
D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2