According to a recent article published in The New England Journal of Medicine, levels of expression of the protein ZAP-70 predicts the aggressiveness of chronic lymphocytic leukemia in younger patients and may help to individualize treatment options.

Chronic lymphocytic leukemia (CLL), also referred to as acute lymphoblastic leukemia, is a cancer involving the lymph (immune) system, which includes lymph nodes, blood and blood vessels found throughout the body, as well as the spleen, thymus and tonsils. This cancer is found in high quantities throughout circulating blood and in bone marrow (spongy material inside large bones that produces blood forming cells). CLL is characterized by the production of atypical lymphocytes. Lymphocytes are specialized immune cells, of which there are two types: B and T-cells. These cells are produced in the bone marrow and each has a very specific function in aiding the body to fight infection. The large majority of CLL cases involve mature B-lymphocytes that tend to live much longer than normal, accumulating in the blood, bone marrow, lymph nodes and spleen. This results in overcrowding of these areas, suppressing the formation and function of blood and immune cells that are normally present. Additionally, the cancerous lymphocytes themselves do not function normally, leading to a further decrease in the ability of the body to fight infection. CLL is considered a slow-growing or low-grade cancer.

Standard treatment options for CLL may include chemotherapy, radiation therapy, biologic therapy, and/or high-dose therapy and stem cell transplantation. Since CLL can be such a slow-growing cancer, treatment may also be delayed until signs of disease progression. Researchers are continuing to evaluate associations between disease characteristics and the aggressiveness of CLL, as some patients can live with the disease for years without treatment or signs of progression, while others benefit from immediate treatment. One test that has been associated with the aggressiveness of CLL is the expression of part of a gene referred to as an unmutated immunoglobulin heavy-chain variable-region gene (IgVH). However, research is ongoing in order to determine an even more accurate predictor of aggressiveness, so that patients with more aggressive forms of CLL may be treated early with more intense therapy, while patients with less aggressive forms of CLL may be spared unnecessary treatment.

Researchers affiliated with the Chronic Lymphocytic Leukemia Research Consortium recently conducted a clinical study evaluating the expression of a protein referred to as ZAP-70 and its potential relationship to the aggressiveness of CLL. The study included 307 patients with an average age of 52 years who were tested for ZAP-70, as well as mutations in the IgVH gene. In the group of patients who did not express ZAP-70, the time from diagnosis of CLL to initial treatment was 11 years in those with a mutated IgVH gene and 7.1 years in those with an unmutated IgVH gene. In the group of patients who did express ZAP-70, the time from diagnosis of CLL to initial treatment was only 2.8 years for those with an unmutated IgVH gene and 4.2 years for those with a mutated IgVH gene.

The researchers concluded that the expression of ZAP-70 strongly predicts the aggressiveness of CLL, as patients who did not express the protein had a significantly longer period of time between diagnosis and the need for treatment compared to those who did express the protein, regardless of the IgVH status. Patients diagnosed with CLL may wish to speak with their physician about the risks and benefits of being tested for ZAP-70 and how the results may affect their treatment decisions.

Reference: Rassenti LZ, Huynh L, Toy TL, et al. ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. The New England Journal of Medicine. 2004; 351: 893-901.

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