BCL-2 J(H) REARRANGEMENTS IN CIRCULATING B-CELLS OF HEALTHY BLOOD-DONORS AND PATIENTS WITH NONMALIGNANT DISEASES/

Purpose: To answer the question whether t(14;18)-positive cells can be detected by polymerase chain reaction (PCR) in the peripheral blood o f healthy blood donors and patients with nonmalignant diseases. Patien ts and Methods: Peripheral-blood mononuclear cells (PBMNC) from health y donors (n = 36) and patients with nonmalignant diseases (n = 21) wer e examined by two-step PCR for the detection of t(14;18)-positive cell s with a breakpoint within the major breakpoint region (MBR). Approxim ate numbers of t(14;18)-positive cells were determined using limiting dilution assays, as well as the stochastic multiple-tube approach. Res ults: We were able to detect t(14;18)-positive cells in PBMNC of appro ximately 50% of healthy donors and patients with nonmalignant diseases if DNA amounts up to 10 mu g were tested. Compared with 17 t(14;18)-p ositive patients being in complete remission after radiotherapy for lo w-stage malignant follicular lymphoma, the majority of 26 healthy dono rs 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 nucleot ide sequence analysis was detected. In one healthy individual, four di fferent t(14;18)-positive cell clones were found in nine samples obtai ned over 5 years. Conclusion: The occurrence of the t(14;18) transloca tion is not restricted to follicular lymphoma cells. In healthy donors , long-lived t(14;18)-positive cells can be detected by PCR if the sen sitivity is high enough. Based on nucleotide sequence analysis, the t( 14;18) DNA fragments detected in healthy donors cannot be distinguishe d from those found in follicular lymphomas. (C) 1996 by American Socie ty of Clinical Oncology.