CBL-MZ is not a single biological entity: evidence from genomic analysis and prolonged clinical follow-up

The term "clonal B cell lymphocytosis of marginal zone origin" (CBL-MZ) 1,2 has recently been suggested for asymptomatic individuals whose routine blood count shows a persistent modest lymphocytosis that is usually accompanied by bone marrow involvement. This immunophenotype is suggestive of marginal zone/postgerminal center derivation, but no other features of a chronic B cell lymphoproliferative disorder are found, other than a low-level paraprotein in some cases. Cases with a clonal lymphocyte count ,5 3 10 9 /L would fall within the revised World Health Organization (WHO) category of non-chronic lymphocytic leukemia-type monoclonal B-cell lymphocytosis. In 3 previous series of CBL-MZ consisting of 102, 53, and 16 cases with median follow-ups (FUs) of 60, 34, and 44 months, respectively, 1,3,4 the overall incidence of progression was 15.7%, with the majority (11.1%) developing splenomegaly that frequently did not require treatment. However, it remains unclear whether CBL-MZ is the precursor to 1 or several well-defined WHO entities and what factors predict disease progression. To address this, we performed a genomic analysis of a well-characterized cohort of CBL-MZ cases with long FU and provide evidence to show that CBL-MZ is not a single biological entity.