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B-cell chronic lymphocytic leukemia (also known as “chronic lymphoid leukemia” or “CLL”), is a type of leukemia, or cancer of the white blood cells (lymphocytes). CLL affects a particular lymphocyte, the B cell, which originates in the bone marrow, develops in the lymph nodes, and normally fights infection. In CLL, the DNA of a B cell is damaged, so that it can’t fight infection, but it grows out of control and crowds out the healthy blood cells that can fight infection.
CLL is an abnormal neoplastic proliferation of B cells. The cells accumulate mainly in the bone marrow and blood. Although not originally appreciated, CLL is now felt to be identical to a disease called small lymphocytic lymphoma (SLL), a type of non-Hodgkin’s lymphoma which presents primarily in the lymph nodes. The World Health Organization considers CLL and SLL to be “one disease at different stages, not two separate entities”.[1]
CLL is a disease of adults. Most (>75%) people newly diagnosed with CLL are over the age 50, and the majority are men. In the United States during 2007, it is estimated there will be 15,340 new cases diagnosed and 4,500 deaths[2], but because of prolonged survival, many more people are living with CLL.[citation needed]
Most people are diagnosed without symptoms as the result of a routine blood test that returns a high white blood cell count, but as it advances CLL results in swollen lymph nodes, spleen, and liver, and eventually anemia and infections. Early CLL is not treated, and late CLL is treated with chemotherapy and monoclonal antibodies. Survival varies from 5 years to more than 25 years. It is now possible to diagnose patients with short and long survival more precisely by examining the DNA mutations, and patients with slowly-progressing disease can be reassured and may not need any treatment in their lifetimes.[3]
Staging, determining the extent of the disease, is done with the Rai staging system or the Binet classification (see details[4]) and is based primarily on the presence, or not, of a low platelet or red cell count. Early stage disease does not need to be treated.
Recent publications suggest that two[5] or three[6] prognostic groups of CLL exist based on the maturational state of the cell. This distinction is based on the maturity of the lymphocytes as discerned by the immunoglobulin variable-region heavy chain (IgVH) gene mutation status.[7] High risk patients have an immature cell pattern with few mutations in the DNA in the IgVH antibody gene region whereas low risk patients show considerable mutations of the DNA in the antibody gene region indicating mature lymphocytes.[8]
Since assessment of the IgVH antibody DNA changes is difficult to perform, the presence of either cluster of differentiation 38 (CD38) or Z-chain–associated protein kinase-70 (ZAP-70) may be surrogate markers of high risk subtype of CLL.[7] Their expression correlates with a more immature cellular state and a more rapid disease course.
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