Three-fold higher frequency of circulating chronic lymphocytic leukemia-like B-cell clones in patients with...

Philadelphia chromosome-negative Myeloproliferative neoplasms (Ph^-MPN) are accompanied by a markedly increased risk for development of chronic lymphocytic leukemia (CLL) compared to the general population. However, the pattern of onset and the biological characteristics of CLL in patients with coexistent Ph^-MPN are highly heterogeneous rendering questionable if the above association reflects a causal relationship between the two disorders or merely represents a random event. By analyzing 82 patients with Ph^-MPN and 100 age-matched healthy individuals we demonstrate that MPN patients have an almost threefold higher prevalence of, typically low-count, CLL-like monoclonal B lymphocytosis (MBL) compared to normal adults. The clone size remained unaltered during the disease course and unaffected by the administration of hydroxycarbamide, whereas no patient with Ph^-MPN/MBL progressed to CLL during a median follow up of 4 years. Monoclonal B cells in Ph^-MPN/MBL patients and normal individuals and in four more patients with coexistence of overt CLL and MPN displayed heterogeneous biological characteristics, while the JAK2V617F mutation was absent in isolated lymphocytes from Ph^-MPN patients with coexistence of CLL. Despite its clinical and biological variability, the increased incidence of MBL in Ph^-MPN patients along with the one reported for CLL further enforces the notion of a shared pathophysiology among the two malignancies via a common genetic link and/or microenviromental interactions.