Causes

Between 1973 and 1990, the number of acute lymphocytic leukemia cases in children under 15 rose by 27%. The causes of the disease are not known, but experts believe that ALL develops from a combination of genetic, biologic, and environmental factors.

Genetic Factors

Advances in genetic technologies have allowed identification of a number of mutations associated with ALL. Missing or defective genes that suppress tumors are responsible for some of these cases. Identifying specific genetic groups is allowing doctors to determine how aggressive a specific case is and eventually could provide targets for developing highly specific treatments.

Translocations. Up to 65% of leukemias contain genetic rearrangements, called translocations, in which some of the genetic material (genes) on a chromosome may be altered, or shuffled, between a pair of chromosomes.

  • For example, the most common genetic injury in ALL is t(12;21), which means a translocation with a genetic shift occurred between chromosome 12 and 21. This translocation is also referred to as TEL-AML1 fusion. It occurs in about 20% of patients with ALL. Researchers believe that this translocation may occur during fetal development in some patients.
  • About 20% of adults and about 5% of children with ALL have a genetic abnormality called the Philadelphia (Ph) chromosome (t(9;22)).
  • Another important chromosome translocation is t(4;11) involving the MLL gene, also called HRX or ALL-1.

Ikaros. A defective gene known as Ikaros, which regulates lymphocyte development, may play a major role in childhood ALL.

MTHFR. Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in folate metabolism. Children with certain variations in the gene for MTHRF have a reduced risk of developing ALL. Variations in the MTHRF gene may also influence response to antifolate chemotherapy.

Environmental Factors

Radiation. Exposure to repeated or high doses of ionizing radiation, which includes x-rays and gamma rays, has long been known to increase the chances of developing leukemia. Specifically, radiation for certain cancer treatments is a known cause of future leukemia.

Infections. Researchers are studying a number of viruses or other infectious substances that may trigger the leukemia, particularly in genetically susceptible children. One researcher suggests, in fact, that a cluster of leukemia cases reported near a nuclear plant may not be due to radiation, as widely believed, but to increased exposure to viruses or infectious organisms brought in by a migrant work force. This is supported by clusters of ALL observed in different small geographical areas where inward migration rates were high. The infectious etiology hypothesis is further supported by a 2004 study that showed a strong association between changes in county populations and the incidence of childhood ALL.

Special viruses called retroviruses, or RNA tumor viruses, cause leukemia in animals. The first of these viruses associated with human leukemia was human thymic leukemia virus -1 (HTLV-1), which may be responsible for some cases of adult acute T-cell leukemia. A strong viral or infectious suspect for ALL, however, has not yet emerged.

Chemicals. To determine whether exposure to specific chemicals causes or increases the risk for leukemia is a daunting challenge. About 75,000 synthetic chemicals were introduced in the first half of the century. In addition, investigators must study the emissions from cars, the pesticides in foods and in neighborhoods, and the runoffs in drinking water.

Electromagnetic Fields. Some studies have reported an association between leukemia and high levels of electromagnetic radiation (EMR), although this is controversial. Lower levels of radiation (e.g., living near power lines, video screen emissions, small appliances, cell phones) are unlikely to pose any cancer risk.

Review Date: 12/17/2005
Reviewed By: Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital