BCL-2/JH rearrangements in circulating B cells of healthy blood donors and patients with nonmalignant diseases.
OBJECTIVE
To answer the question whether t(14;18)-positive cells can be detected by polymerase chain reaction (PCR) in the peripheral blood of healthy blood donors and patients with nonmalignant diseases.


METHODS
Peripheral-blood mononuclear cells (PBMNC) from healthy donors (n = 36) and patients with nonmalignant diseases (n = 21) were examined by two-step PCR for the detection of t(14;18)-positive cells with a breakpoint within the major breakpoint region (MBR). Approximate numbers of t(14;18)-positive cells were determined using limiting dilution assays, as well as the stochastic multiple-tube approach.


RESULTS
We were able to detect t(14;18)-positive cells in PBMNC of approximately 50% of healthy donors and patients with nonmalignant diseases if DNA amounts up to 10 microg were tested. Compared with 17 t(14;18)-positive patients being in complete remission after radiotherapy for low-stage malignant follicular lymphoma, the majority of 26 healthy donors were found to have significantly lower numbers of t(14;18)-positive cells circulating in the peripheral blood. In the case of six healthy donors, more than one t(14;18) DNA fragment based on size and nucleotide sequence analysis was detected. In one healthy individual, four different t(14;18)-positive cell clones were found in nine samples found over 5 years.


CONCLUSIONS
The occurrence of the t(14;18) translocation is not restricted to follicular lymphoma cells. In healthy donors, long-lived t(14;18)-positive cells can be detected by PCR if the sensitivity is high enough. Based on nucleotide sequence analysis, the t(14;18) DNA fragments detected in healthy donors cannot be distinguished from those found in follicular lymphomas.
Dölken
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Klinik und Poliklinik für Innere Medizin C, Hämatologie und internistische Onkologie, Ernst-Moritz-Arndt-Universität, Sauerbruchstr/Diagnostikzentrum, Greifswald, Germany.
Illerhaus
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G
Hirt
C
C
Mertelsmann
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D001782:Blood Donors; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured