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Pathophysiology and genetic features of chronic lymphocytic leukemia

Kanti R Rai, MD
Stephan Stilgenbauer, MD
Section Editor
Richard A Larson, MD
Deputy Editor
Rebecca F Connor, MD


Chronic lymphocytic leukemia (CLL) is one of the chronic lymphoproliferative disorders (lymphoid neoplasms). According to the current WHO classification, B cell CLL is considered to be identical (ie, one disease with different manifestations) to the mature (peripheral) B cell neoplasm small lymphocytic lymphoma (SLL) [1]. It is characterized by a progressive accumulation of functionally incompetent lymphocytes, which are usually monoclonal in origin.

The pathophysiology and molecular biology of B cell CLL/SLL will be reviewed here. The incidence, epidemiology, clinical manifestations, diagnosis, and treatment of CLL/SLL and its variants (T cell CLL, prolymphocytic leukemia), and the role of hematopoietic cell transplantation are discussed separately. (See "Clinical presentation, pathologic features, diagnosis, and differential diagnosis of chronic lymphocytic leukemia" and "Hematopoietic cell transplantation in chronic lymphocytic leukemia" and "Clinical manifestations, pathologic features, and diagnosis of small lymphocytic lymphoma".)


The molecular pathogenesis of chronic lymphocytic leukemia (CLL) is a complex, multistep process leading to the replication of a malignant clone of B-lymphocytes (figure 1). While some steps in this pathway have been elucidated, many remain unknown. It is believed that virtually all CLL cases are preceded by a premalignant B cell proliferative disorder known as monoclonal B cell lymphocytosis (MBL). MBL with a CLL-phenotype is present in 5 to 15 percent of the population above the age of 60 and progresses to CLL/SLL or a related malignancy at a rate of approximately 1 percent per year [2,3]. (See "Approach to the adult with lymphocytosis or lymphocytopenia", section on 'Monoclonal B cell lymphocytosis'.)

The pathogenesis of CLL can be conceptualized as two sequential processes:

Establishment of MBL – While the inciting event is unknown, MBL appears to develop as the result of multiple factors, such as response to antigenic stimulation, microenvironmental support, gene mutations, epigenetic modification, and cytogenetic abnormalities. The result is a clone of B cells with a CLL phenotype.


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Literature review current through: Sep 2016. | This topic last updated: May 4, 2016.
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