Disease Progression in Monoclonal B-Cell Lymphocytosis Is Independent of VH Mutation Status

A monoclonal B-cell Lymphocytosis (MBL) is detected in the peripheral blood of around 3% of otherwise healthy adults, the majority of these have a CLL immunophenotype. We have previously demonstrated that the cells in MBL are indistinguishable from good risk CLL, sharing the same immunophenotypic profile, genetic aberrations and IgVH gene usage. MBL exerts an increasing burden on haematology clinics with over 100 new patients diagnosed per annum in our regional haemato-oncology laboratory. This is largely as a result of the increased tendency to investigate patients with a mild lymphocyosis although 10,000/μL and included 3 patients who progressed to a clinical stage requiring treatment. VH gene usage was different in each of these 3 patients was with VH3-7, VH4-34 and VH5-51 identified, the levels of SHM were 5.8, 4.0 and 5.3% respectively. Follow-up data shows that a deletion of ATM was detected at progression in one of these patients. In conclusion, we show that MBL is predominantly mutated and that progression to CLL is independent of mutational status. Other prognostic markers, particularly assessment of chromosomal aberrations, may be informative but this would probably require cell selection to increase sample purity. Our data suggests that current prognostic markers are not effective at predicting outcome in MBL and periodic monitoring is required.