Leukemia

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Causes

Although researchers have studied the many cellular changes associated with leukemia, it is unknown why these changes occur. It is likely that certain risk factors are involved. Many factors (e.g., age, genetics) are unmodifiable (beyond control). Other factors (e.g., environmental, lifestyle-related variables) are more controllable (modifiable).

It is now known that all cancers, including leukemia, begin as a mutation in the genetic material—the DNA (deoxyribonucleic acid)—within certain cells. The external or internal causes of such change probably add up over a lifetime. Leukemia begins when one or more white blood cells experience DNA loss or damage. Those errors are copied and passed on to subsequent generations of cells. The abnormal leukemic cells remain in an immature blast form that never matures properly. They do not die off like normal cells, but tend to multiply and accumulate within the body.

DNA errors also may occur in the form of translocations—damage produced when part of one chromosome becomes displaced and attached to another chromosome. Translocations disrupt the normal sequencing of the genes. As a result, oncogenes (cancer-promoting genes) on the chromosomes may be "switched on," while tumor suppressors (cancer-preventing genes) may be switched off. Many leukemias contain translocations that affect the blood cell chromosomes. Physicians often test for these translocations to help diagnose leukemia, determine a patient's prognosis, and identify cancer recurrence.

Risk Factors

Numerous risk factors may be responsible for DNA damage within the blood cells. The risk factors believed to have the strongest associations with leukemia include the following:

• Age - Roughly 60–70% of leukemias occur in people who are older than 50.

• Radiation–The risk of chronic myelogenous leukemia (CML) is increased among people who have been exposed to high doses of radiation (for example, atomic bomb survivors in Japan, people who lived near the nuclear reactor accident in Chernobyl, and armed forces who participated in American nuclear detonations during the late 1950s). It is important to note, however, that standard diagnostic x-rays pose little or no increase in leukemia risk.

• Chemicals–The risk for acute leukemia is increased 20-fold among workers with long-term exposure to benzene. Risk also is increased among workers exposed to some other solvents, herbicides, and pesticides. Agricultural chemicals, in particular, have been linked with an increased risk of chronic lymphocytic leukemia (CLL). In addition, some reports suggest that leukemia risk may be increased in workers exposed to dioxin, styrenes, butadienes, or ethylene oxides.

• Viruses–The human T-cell leukemia virus I (HTLV-I) is related to acute T-cell leukemia. This type of leukemia is well documented in parts of the Caribbean and Asia, but it is uncommon in the United States and Europe. Higher rates of leukemias also have been reported in workers who are exposed to animal viruses (e.g., butchers, slaughterhouse workers, veterinary practitioners).

• Genetics–Leukemia risk is increased 15-fold among children with Down's syndrome, which is a genetically linked chromosomal abnormality (usually an extra copy of chromosome 21). Three rare inherited disorders—Fanconi's anemia, Bloom's syndrome, and ataxia telangiectasia—also have an increased risk for leukemia.

  In addition, leukemia varies among racial and ethnic groups with different genetic make-ups. For example, rates of lymphoma and leukemia (e.g., chronic lymphocytic leukemia, CLL) are especially high in some Jewish populations, whereas Asian populations rarely develop CLL. First-degree relatives (e.g., parents, children, siblings) of CLL patients have a 2- to 4-fold increased risk for this cancer.

  Recent studies have shown that, in some types of leukemia (e.g., AML), genetics also may play a role in the risk for recurrence of the disease.

• Cigarette smoking–Cigarette smoking is a known lifestyle-related risk factor for leukemia. Potential leukemia-causing chemicals in tobacco smoke include benzene, polonium-210, and polycyclic aromatic hydrocarbons (PAHs). These carcinogens (cancer-causing substances) are absorbed by the lungs and are spread via the bloodstream. It is estimated that one in four cases of acute myelogenous leukemia (AML) is the result of cigarette smoking.
  
  
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• Cancer therapy–Individuals who have received chemotherapy and radiation therapy for previous cancers have a slightly greater chance of getting secondary leukemia (leukemia that arises after therapy). Acute myelogenous leukemia (AML) has been reported after chemotherapy and/or radiotherapy for various solid tumors (breast cancer, ovarian cancer), blood malignancies, and nonmalignant conditions. The chemotherapeutic agents most often associated with secondary leukemias are procarbazine, chlorambucil, etoposide, mechlorethamine, teniposide, and cyclophosphamide. The risk is increased when these drugs are combined with radiation therapy. Many secondary leukemias are AMLs that develop within 9 years after treatment of Hodgkin's disease, non-Hodgkin's lymphoma, or childhood CLL. Further chemotherapy often is ineffective in patients with secondary AML; their prognosis is less favorable that that of typical AML patients.

• Other medical therapy and events–Use of the antibiotic chloramphenicol has been linked with the development of childhood leukemia. Other medications, such as growth hormones and phenylbutazone, also have reportedly shown some associations with leukemia. Leukemias and lymphomas have been observed in recipients of organ transplants, and certain immunodeficiency syndromes are associated with leukemias (e.g., infantile X-linked agammaglobulinemia and lymphatic leukemia).

A number of reports have suggested that strong electromagnetic fields (EMF) may be a risk factor for leukemia, although other investigations have failed to confirm these findings. Therefore, National Cancer Institute (NCI) researchers are performing several large-scale studies to try to answer the question of whether or not EMF exposure poses a cancer risk. To date, most publications indicate that leukemia is not related to EMF exposure.

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