title: Cells carrying nonlymphoma-associated bcl-2/IgH rearrangements (NLABR) are phenotypically related to follicular lymphoma and can establish as long-term persisting clonal populations.
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.
authors.affiliation: Divisione di Ematologia Dipartimento di Medicina ed Oncologia Sperimentale, Universita' di Torino-A. O. San Giovanni Battista della Citta' di Torino, Torino, Italy. marco.ladetto@unito.it
authors.forename: Marco
authors.initials: M
authors.lastname: Ladetto
authors.forename: Barbara
authors.initials: B
authors.lastname: Mantoan
authors.forename: Federica
authors.initials: F
authors.lastname: De Marco
authors.forename: Daniela
authors.initials: D
authors.lastname: Drandi
authors.forename: Chiara
authors.initials: C
authors.lastname: Aguzzi
authors.forename: Monica
authors.initials: M
authors.lastname: Astolfi
authors.forename: Sonia
authors.initials: S
authors.lastname: Vallet
authors.forename: Irene
authors.initials: I
authors.lastname: Ricca
authors.forename: Maria
authors.initials: M
authors.lastname: Dell' Aquila
authors.forename: Gloria
authors.initials: G
authors.lastname: Pagliano
authors.forename: Luigia
authors.initials: L
authors.lastname: Monitillo
authors.forename: Berardino
authors.initials: B
authors.lastname: Pollio
authors.forename: Loredana
authors.initials: L
authors.lastname: Santo
authors.forename: Carmen
authors.initials: C
authors.lastname: Cristiano
authors.forename: Alberto
authors.initials: A
authors.lastname: Rocci
authors.forename: Roberto
authors.initials: R
authors.lastname: Francese
authors.forename: Chiara Lobetti
authors.initials: CL
authors.lastname: Bodoni
authors.forename: Alessandra
authors.initials: A
authors.lastname: Borchiellini
authors.forename: Piercarla
authors.initials: P
authors.lastname: Schinco
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
authors.forename: Corrado
authors.initials: C
authors.lastname: Tarella
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002469:Cell Separation; D002999:Clone Cells; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008224:Lymphoma, Follicular / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic
chemical_list: D007143:Immunoglobulin Heavy Chains; D019253:Proto-Oncogene Proteins c-bcl-2