All patients with persistent polyclonal B cell lymphocytosis present Bcl-2/Ig gene rearrangements

The bcl-2 gene belongs to a class of oncogenes involved in the inhibition o f apoptosis. Most follicular lymphomas are associated with the t(14;18) tra nslocation that juxtaposes the bcl-2 gene located on chromosome 18 to the i mmunoglobulin gene locus located on chromosome 14. Consequently, the bcl-2 gene is overly expressed and leads to an accumulation of mature clonal B ce lls. Prolonged survival of the B cell clone appears to be the early event i n tumorigenesis, creating an increased risk of cumulative mutations. Intere stingly, bcl-2/Ig gene rearrangements may be identified in nearly 50% of no rmal individuals but the outcome of normal individuals carrying high levels of t(14;18) is not well defined. Persistent polyclonal B cell lymphocytosi s (PPBL) is a unique polyclonal lymphoproliferative disorder mostly restric ted to women. We have recently demonstrated that PPBL is also associated wi th multiple bcl-2/Ig gene rearrangements. In this report, we have extended our analysis to additional patients and demonstrated that all patients pres ented multiple detectable t(14;18) translocated clones. In addition, Bcl-2 protein expression was increased. Our findings, along with the clinical fea tures of PPBL, make this disorder an exceptional model for the study of B-c ell homeostasis.