Cells carrying nonlymphoma-associated bcl-2/IgH rearrangements (NLABR) are phenotypically related to follicular lymphoma and can establish as long-term persisting clonal populations.
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.
Ladetto
Marco
M
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
Mantoan
Barbara
B
De Marco
Federica
F
Drandi
Daniela
D
Aguzzi
Chiara
C
Astolfi
Monica
M
Vallet
Sonia
S
Ricca
Irene
I
Dell' Aquila
Maria
M
Pagliano
Gloria
G
Monitillo
Luigia
L
Pollio
Berardino
B
Santo
Loredana
L
Cristiano
Carmen
C
Rocci
Alberto
A
Francese
Roberto
R
Bodoni
Chiara Lobetti
CL
Borchiellini
Alessandra
A
Schinco
Piercarla
P
Boccadoro
Mario
M
Tarella
Corrado
C
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
D007143:Immunoglobulin Heavy Chains; D019253:Proto-Oncogene Proteins c-bcl-2