B-lymphocyte expansion Inherited predisposition to CLL is detectable as sub-clinical monoclonal

ABSTRACT Monoclonal CLL-phenotype cells are detectable in 3.5% of otherwise normal individuals using flow cytometric analysis of CD5/CD20/CD79b expression on CD19-gated B-cells. To determine whether detection of such CLL-phenotype cells is indicative of an inherited predisposition, we examined 59 healthy first-degree relatives of patients from 21 CLL families. CLL-phenotype cells were detected in 8/59 relatives (13.5%), representing a highly significant increase in risk (p=0.00002). CLL-phenotype cell levels were stable with time, and had the characteristics of indolent CLL. Both indolent and aggressive clinical forms were found in family members, suggesting that initiation and proliferation involves distinct factors. The detection of CLL-phenotype cells provides a surrogate marker of carrier status, potentially facilitating gene identification through mapping in families and direct analysis of isolated CLL-phenotype cells. From bloodjournal.hematologylibrary.org by guest on May 30, 2013. For personal use only.