Cells carrying nonlymphoma-associated bcl-2/IgH rearrangements (NLABR) are phenotypically related to follicular lymphoma and can establish as long-term persisting clonal populations

Exp Hematol. 2006 Dec;34(12):1680-6. doi: 10.1016/j.exphem.2006.08.008.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Separation
  • Clone Cells
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Heavy Chains / metabolism
  • Immunophenotyping
  • Leukocytes, Mononuclear / metabolism*
  • Lymphoma, Follicular / genetics*
  • Male
  • Middle Aged
  • Polymerase Chain Reaction / methods
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Translocation, Genetic*


  • Immunoglobulin Heavy Chains
  • Proto-Oncogene Proteins c-bcl-2