Chronic lymphocytic leukaemia

Cancer research · Chronic lymphocytic leukemia

Current advances in the biology of CLL have profoundly enhanced our ability to identify patients who are at higher risk for disease progression and our capacity to treat patients with drugs that selectively target distinctive phenotypic or physiological features of CLL.

Chronic lymphocytic leukaemia (CLL) is a malignancy of CD5^+ B cells that is characterized by the accumulation of small, mature-appearing lymphocytes in the blood, marrow and secondary lymphoid tissues, resulting in lymphocytosis, leukaemia cell infiltration of the marrow, lymphadenopathy and splenomegaly. Genetic factors contribute to the development of CLL; although CLL is the most common adult leukaemia in western countries, it is less common in Asia and relatively rare in Japan and Korea, even among Japanese people who immigrate to western counties. CLL can be divided into two main subsets, which differ in their clinical behaviour. These subsets are distinguished by whether CLL cells express an unmutated or mutated immunoglobulin heavy-chain variable region gene (IGHV), reflecting the stage of normal B cell differentiation from which they originate. Patients with CLL cells that express an unmutated IGHV typically have more-aggressive disease than patients with CLL cells that express a mutated IGHV. CLL cells with mutated IGHV arise from a post-germinal centre B cell that expresses immunoglobulin that has undergone somatic hypermutation and, in some cases, also immunoglobin isotype switching. It should be emphasized that the high level of somatic mutations that arise in IGHV in the germinal centre are a natural part of affinity maturation of antibodies and, unlike mutations in other genes, are not pathological. The tumours are simply reflecting the stage of maturation of the parental B cell. In addition, some CLL cells have been described that are similar to unmutated IGHV CLL, but originate from B cells with limited somatic mutation, such as CLL with immunoglobulin heavy chains encoded by mutated IGHV3-21 and immunoglobulin light chains encoded by unmutated IGLV3-21.

Understanding the underlying molecular mechanisms of CLL facilitates risk stratification and the development of targeted therapies, improving patient outcomes.

Evidence level: Számítógépes vagy elméleti. Modellből vagy adatbányászatból származó jel.

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