What Causes Mantle Cell Lymphoma?

Mantle cell lymphoma (MCL) is a rare form of cancer, comprising approximately 6 percent of all cases of lymphoma in the United States (Lymphoma & Leukemia Society [LLS]). MCL affects the B lymphocytes, a type of white blood cell that fights infections. A genetic mutation causes two chromosomes to switch places, resulting in uncontrolled cell growth. What causes the chromosomes to change places, however, is unknown.

Definition

• MCL is a rare type of non-Hodgkins lymphoma, or a cancer of the lymphatic system (Cancerbackup). The lymphatic system manufactures white blood cells (lymphocytes), the key components of the body's immune system (LLS). The lymphocytes travel throughout the body in a fluid called lymph. From the lymph system, the lymphocytes enter the bloodstream or tissues to fight foreign bodies such as viruses or bacteria. The lymph nodes, clustered in the underarms, groin and neck, produce three types of lymphocytes: B lymphocytes, T lymphocytes and natural killer cells (LLS). The B and T lymphocytes identify foreign bodies and coat them in a protein, making them a target for the killer cells. MCL specifically affects the B lymphocytes (Cancerbackup). B lymphocytes are produced by follicles found on the outer region, or cortex, of the lymph nodes (LLS). The newly produced B cells reside in the mantle, located on the outer zone of the follicles. T lymphocytes are found in the spaces between the follicles.

Causes

• A chromosomal mutation in B lymphocytes called reciprocal translocation causes 85 percent of all MCL cases (LLS). Although the exact cause for the genetic mutation is unknown, researchers have pinpointed that in the majority of MCL cases, chromosomes 11 and 14 have reversed positions. This translocation results in the overproduction of a protein called cyclin D1, which stimulates cell growth. The B lymphocytes carrying the translocated genes grow uncontrollably, eventually accumulating into tumors in the lymph nodes. These cancerous cells can then be carried by the lymph system throughout the body. A small percentage of MCL cases do not have the genetic mutation. Additionally, other mutations cause excessive production of other proteins regulating cell growth (cyclin D2 and cyclin D3) that also may result in MCL (LLS). MCL can occur at any age but most often occurs in people older than 60 years. It is three times more common in men than women (Cancerbackup).

Symptoms

• The first sign of MCL is enlarged but painless lymph nodes in the neck, armpit or groin (Cancerbackup). Loss of appetite, fatigue, unexplained night sweats, unexplained fever and weight loss are other symptoms. MCL may spread from the lymph nodes to other organs such as the liver, spleen or bone marrow. Gastrointestinal tumors are also common.

Treatment

• Treatment often consists of a combination of multiple therapies. Chemotherapy is the standard treatment, with the exact regimen determined by the stage of the MCL and the age and general health of the patient (Cancerbackup). Radiation therapy is also used, along with bone marrow or stem cell transplantation. Stem cell therapy may be combined with high doses of chemotherapy, but this strategy is typically reserved for younger patients (younger than 50 years) because of severe side effects. Steroids may be administered to control side effects associated with chemotherapy. Targeted therapies, such as monoclonal antibodies and other experimental agents, are under investigation. These therapies recognize proteins specific to the cancerous cells and stimulate the body's natural immune system to fight the tumors (Cancerbackup).

Prognosis

• Chemotherapy is often effective and most patients will respond initially (LLS). However, relapse and disease progression occur frequently, and the cancerous cells often develop resistance to the chemotherapeutic agents. The average length of progression-free survival, or the time a patient lives without the cancer worsening, is 20 months, and the average length of survival is four years after the initial diagnosis.