What Causes Acute Lymphoblastic Leukemia?
A short discussion of the possible causes of acute lymphoblastic leukemia, whose incidence appears to be on the rise.
Between 1973 and 1990, the number of acute lymphoblastic leukemia cases in children under 15 rose by 27%. The causes of the disease and this dramatic increase are not known, but experts believe that ALL develops from a combination of genetic and environmental factors.
Under investigation are viruses, about 75,000 new synthetic chemicals introduced in the first half of the century, the emissions from cars, the pesticides in foods and in neighborhoods, and the runoffs in drinking water.
Acute lymphoblastic leukemia and Genetic Factors
A number of genetic mutations associated with ALL have been identified. A new study reports on a defective gene known as Ikaros, which regulates lymphocyte development and may be responsible for ALL in infants. About 20% of adults and about 5% of children with ALL have a genetic abnormality called the Philadelphia (Ph) chromosome.
Children with the genetic abnormality called the Philadelphia (Ph) chromosome have a more severe form of ALL. The chromosome does not appear to be as harmful in most ALL adults who carry it. About 20% of people with acute lymphoblastic leukemia have a genetic defect called TEL-AML1, which responds well to chemotherapy. A defect called ETV6 also responds well.
Those referred to as E2A-PEX1, MLL, or BCR-ABL may require very aggressive therapy. Missing or defective genes that suppress tumors are responsible for some cases of ALL.
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 (a process called translocation). For example the t(12;21) means a translocation with a genetic shift between chromosome 12 and 21; this has been found to be the most common genetic lesion in ALL, occurring in approximately 20% of patients. Those with this translocation have an excellent prognosis.
The t(4;11) is the most common translocation in children under one year and, unfortunately, it carries a poor outlook. A less translocation, t (9;22), also indicates a poor outlook. About 30% of adult who carry the Philadelphia (Ph) chromosome also have the t(9;22) translocation, which worsens the prognosis in an otherwise less serious condition in adults.
Causes of Causes of Acute lymphoblastic leukemia: Environmental Assaults
Ionizing radiation, which includes x-rays and gamma rays, has so much energy that the rays can pass through the human body and disrupt chemical bonds. Exposure to repeated or high doses of ionizing radiation increases the chances of developing leukemia.
Industrial and Pharmaceutical Chemicals
Certain chemicals are known cause leukemia; benzene is the best-researched and is now known to cause acute leukemia (most often acute myeloid). Certain drugs used in chemotherapy for other cancers, particularly alkylating agents, such as melphalan (Alkeran) or platinum-based chemotherapies used in ovarian cancer, are known to increase the risk of acute leukemia. Other drugs, such as chloramphenicol and phenylbutazone, may heighten risk as well.
One study of a town in which a cluster of ALL cases were reported observed that the town was located near a large agricultural area where pesticides were heavily used.
Although no evidence exists for a cause-and-effect relationship, another recent study of three Irish counties reported that exposure to agricultural chemicals was associated with a higher incidence in chronic leukemia and non-Hodgkin’s disease, particularly in farmers who did not wear protective masks when spraying pesticides.
Some experts believe that some cases of childhood ALL may result from an abnormal response to infections. Clusters of ALL in children have been observed in different small geographical areas, particularly in regions where inward migration rates were high, suggesting that infections may play a role in the disease.
A recent Swedish study supporting a possible infectious trigger reported that the prevalence of childhood lymphoblastic leukemia was much higher in densely populated areas than in other parts of the country. Scientists have known for years that special viruses called retroviruses, or RNA tumor viruses, cause leukemia in animals. The first of these viruses associated with leukemia in humans was human thymic leukemia virus -1 (HTLV-1), which may cause genetic changes that result in some cases of adult acute T-cell leukemia.