1. Cells carrying nonlymphoma-associated bcl-2/IgH rearrangements (NLABR) are phenotypically related to follicular lymphoma and can establish as long-term persisting clonal populations.
- Author
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Ladetto M, Mantoan B, De Marco F, Drandi D, Aguzzi C, Astolfi M, Vallet S, Ricca I, Dell' Aquila M, Pagliano G, Monitillo L, Pollio B, Santo L, Cristiano C, Rocci A, Francese R, Bodoni CL, Borchiellini A, Schinco P, Boccadoro M, and Tarella C
- Subjects
- Adult, Aged, Aged, 80 and over, Cell Separation, Clone Cells, Female, Follow-Up Studies, Humans, Immunoglobulin Heavy Chains metabolism, Immunophenotyping, Male, Middle Aged, Polymerase Chain Reaction methods, Proto-Oncogene Proteins c-bcl-2 metabolism, Immunoglobulin Heavy Chains genetics, Leukocytes, Mononuclear metabolism, Lymphoma, Follicular genetics, Proto-Oncogene Proteins c-bcl-2 genetics, Translocation, Genetic
- Abstract
Objective: Nonlymphoma-associated bcl-2/IgH rearrangements (NLABRs) are frequently amplified by PCR in blood of lymphoma-free subjects (LFS), but the temporal kinetics and phenotypic nature of NLABR-positive cells are unknown. To address these issues we prospectively monitored a panel of NLABR-positive LFS., Methods: LFS have been studied by nested PCR, real-time PCR, and DNA sequencing. Cell selection studies were also performed to define the nature of NLABR-bearing clones., Results: Of 125 donors, 16 (12.8%) were found to be bcl-2/IgH positive and were monitored at least every 6 months for a median time of 22 months (range 6-50). In half of the subjects the same NLABR detected initially was again reamplified at follow-up thrice or more. In 5, the same NLABR was constantly amplified in every follow-up sample. With a median follow-up of 22 months (range 9-50), no stable disappearance of a recurrent clone has been so far recorded. Real-time PCR indicated that persistent NLABR-positive clones are stable over time in the same subject. Cell separation studies indicate that NLABRs belong to CD19+, CD5-, CD23-, CD10+/- cells., Conclusions: Our results indicate that NLABR-positive clones are persistent populations phenotypically related to follicular lymphoma (FL). This suggests the existence of a FL-related clonal expansion of undetermined significance, which might be either a premalignant or a nonmalignant counterpart of FL.
- Published
- 2006
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