Laboratory Diagnosis of Chronic Lymphocytic Leukaemia

Chronic lymphocytic leukaemia (CLL) is one of the most common B-lymphoproliferative disorders (B-LPD) and is characterised by an expansion of monoclonal B-cells which are typically small lymphocytes with a narrow rim of cytoplasm and a dense nucleus lacking nucleoli and showing partially aggregated chromatin. The B-cells express CD19, CD5 and CD23 with weak CD20/CD79b and surface immunoglobulin although there is some heterogeneity in expression. Additional markers that are expressed in CLL and can help to distinguish other B-cell disorders include CD200, which is infrequently expressed in mantle cell lymphoma, as well as CD43 and ROR1 which are typically absent in lymphoplasmacytic and marginal-zone origin B-cell disorders. There is no pathognomonic molecular lesion in CLL. Chromosomal copy number variations are a common feature with the loss of 13q14, affecting microRNAs mir-15a/16-1 and potentially resulting in overexpression of BCL2, being an early feature of the disease in the majority of patients. However, genomic studies demonstrate a large array of additional molecular abnormalities with over 40 driver mutations potentially involved in the development of progressive disease. In the absence of extramedullary disease or cytopenia, the presence of circulating monoclonal CLL-phenotype B-cells below the level of 5 × 109/L is termed monoclonal B-cell lymphocytosis (MBL). Bone marrow investigation is not always required for diagnosis as a high proportion of patients are asymptomatic and only require active monitoring. However, it is important to recognise that CLL/MBL is often an incidental finding co-existing with other conditions, including in some cases another B-LPD. Therefore, multidisciplinary analysis of laboratory and clinical features is essential to reach a diagnosis and identify the appropriate clinical management.