Acute Lymphocytic Leukemia - Causes

Causes

Between 1973 - 1990, the number of acute lymphocytic leukemia cases in children under age 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.

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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.

• 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. 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.