Sections View Full Chapter Figures Tables Videos Full Chapter Figures Tables Videos Supplementary Content ++ DEFINITION ++ Chronic lymphocytic leukemia (CLL) is a malignancy of mature B cells characterized by blood and marrow lymphocytosis. Varying degrees of lymphadenopathy, splenomegaly, and blood cytopenias develop as the neoplasm progresses. ++ EPIDEMIOLOGY ++ CLL is the most prevalent adult leukemia in Western societies. The prevalence of CLL in the United States in 2014 was 126,553 patients. There are approximately 15,700 new cases annually. CLL is uncommon before age 40 years and is extremely rare in children or young adults. The incidence of the disease increases logarithmically after age 45 years. Median age at diagnosis is approximately 70 years. CLL is uncommon in Asian countries and in Asians immigrants to the Americas or Europe. ++ ETIOLOGY AND PATHOGENESIS ++ Environmental Factors ++ Radiation or chemotherapy has not been shown to be a risk factor for developing CLL. Exposure to occupational chemicals, such as solvents, paints, or pesticides, has not been established to be a risk factor for CLL. There is a higher frequency of living or working on a farm in patients with CLL compared to those without the disease. ++ Hereditary Factors ++ Familial occurrence is most evident in CLL compared with other leukemias. — Multiple cases of CLL are found within a single family with greater frequency. — Up to 10% of patients with CLL have a first- or second-degree relative with CLL. — First-degree relatives of patients with lymphoplasmacytic lymphoma or Waldenström macroglobulinemia (Chap. 69) have a greater than threefold increased risk of developing CLL. Genetic factors contribute to increased incidence of CLL. — Polymorphisms in the gene encoding CD5 (located at chromosome 11q13), CD38 (located at chromosome 4p15), or tumor necrosis factor-α, and other genes mapping to chromosome 13q21.33-q22.2. ++ Disease Biology ++ CLL cells typically express CD5, CD19, CD23, and low levels of CD20. CLL cells have surface immunoglobulins reactive with self-antigens. CLL cells have defective apoptosis supported by the microenvironment. CLL cells overexpress BCL-2. CLL is characterized by dysregulation in both cellular and humoral immunity. CLL cells depend on constitutive activation of the B-cell receptor pathway for survival; the survival signals are transduced through LYN, PI3K, SYK, and BTK pathways. ++ Monoclonal B-Cell Lymphocytosis ++ CLL has an initial phase referred to as monoclonal B-cell lymphocytosis. In most cases, this is not apparent at diagnosis because it is asymptomatic and is detected by flow cell analysis of blood lymphocytes. Patients have no lymphadenopathy; no splenomegaly; otherwise normal blood counts; and no fever, night sweats, or unexplained weight loss. The incidence of monoclonal B-cell lymphocytosis increases dramatically after 40 years of age. Approximately 15% of healthy individuals, who have first-degree relatives with two or more family members with CLL, have blood monoclonal B cells of the CLL B-cell immunophenotype. The immunophenotype of the monoclonal B cells may be ... GET ACCESS TO THIS RESOURCE Sign In Username Error: Please enter User Name Password Error: Please enter Password Forgot Username? Forgot Password? Sign in via OpenAthens Sign in via Shibboleth Get Free Access Through Your Institution Contact your institution's library to ask if they subscribe to McGraw-Hill Medical Products. What is MyAccess? Create a FREE MyAccess profile to: Use this site remotely Bookmark your favorite content Track your self-assessment progress and more!