Monoclonal B-cell lymphocytosis is characterized by mutations in CLL putative driver genes and clonal heterogeneity many years before disease progression

Monoclonal B-cell lymphocytosis (MBL) is defined as an asymptomatic expansion of clonal B cells with less than 5 × 109/L cells in the peripheral blood and without other manifestations of chronic lymphocytic leukemia (CLL; for example, lymphadenopathy, cytopenias, constitutional symptoms).1 Approximately 1% of the MBL cohort develops CLL per year. Evidence suggests that nearly all CLL cases are preceded by an MBL state. Our understanding of the genetic basis, clonal architecture and evolution in CLL pathogenesis has undergone significant improvements in the last few years. In contrast to CLL, our knowledge of the genetics in MBL is still very fragmented, with few prior studies focused on the status of selected genetic abnormalities. In addition, previous reports have demonstrated the co-existence of two B-cell subclones in a small subset of MBL cases,11 and clonal changes in sequential MBL samples measured by IGHV mutational analysis.