Causes Of Leukemia.

The basic cause of leukemia is unknown; exposure to radiation, chemicals, and certain drugs appears to increase the risk. Viruses, heredity, and chromosomal abnormalities have also been implicated. A rapidly growing body of research strongly suggests that certain genes called oncogenes may be directly involved in the development of many cancers, including leukemia.

Certain chemicals, such as benzene, have long been known to cause damage to bone marrow cells which form the blood, and it is logical to conclude that they can also cause a cancer in those cells. Many drugs, such as the antibiotic chloramphenicol, also can alter bone marrow function, and may be associated with some cases of leukemia. But chemical and drug exposure accounts for only a very small percentage of the total number of leukemias.
Radiation is the one factor that physicians know for certain can cause leukemia, but the incidence of excessive X-ray exposure is currently very small. The Japanese who survived the atomic bombings at Hiroshima and Nagasaki had an increased incidence of leukemia for twenty years after the event, but the rate has slowed down over the last twenty years, approaching that of normal populations. There is no evidence that routine exposure to X rays at the levels currently used for medical diagnosis increases the risk of cancer, including leukemia.

Cancer researchers now believe that genetics and virology, the study of viruses, hold the greatest promise of finding the cause of leukemia. In both fields, efforts are concentrated on determining how alterations of the genetic material cause cancer. In some cases the cancer-causing genes appear to result from damage arising from hereditary influences or problems that occur during cell division. In other instances, the malignant transformation may be the result of a viral infection in normal genes that control cell growth and reproduction.

Research is also concentrating on oncogenes, cancer-causing genes that are part of many people's normal genetic makeup. These genes can apparently be activated under circumstances that have not yet been identified. Oncogene research is being carried out in many centers with the hope that, by identifying and understanding specific oncogenes, people who are considered at risk can be identified long before a cancer begins. The long-term hope is to find a way to block the action of the oncogene and to prevent or limit the growth of its resultant cancer. Although this is a long way in the future and may never become reality, the concept of the oncogene has given scientists a new and fundamental approach to the study of cancer that many believe will yield fruitful results.

The hereditary causes of leukemia are far from being fully understood. A hereditary predisposition to cancer may imply the inheritance of an oncogene. Close relatives of leukemia patients have an increased risk of developing the disease. The greatest statistical risk is found in the identical twin of a child who has an acute leukemia before age eight. Approximately 20 percent of these individuals will develop the disease within one year of their twin's diagnosis. Genetics obviously plays a strong role here. Brothers and sisters of patients with acute leukemia have five times the risk of the general population. Their increased risk is nevertheless quite small. Children with Down's syndrome and other hereditary or genetic diseases associated with damage or modification of the chromosomes have an increased frequency of leukemia. But whether heredity plays a major role in all leukemia cases is an unanswered question.

Finally, leukemia may be caused by other diseases that damage the bone marrow and by the anticancer drugs used in the treatment of a wide variety of cancers. Diseases that cause severe depression of the marrow, such as aplastic anemia, are associated with a high incidence of leukemia. Patients with myelofibrosis, a disease in which the marrow is replaced by fibrous tissue, may later develop chronic granulocytic leukemia.

More common is the increased incidence of leukemia in patients taking anticancer drugs for the treatment of other malignancies. Most of these patients have received cancer chemotherapy over a relatively long period of time. Typically, acute leukemia develops late in the course of the other disease. Although oncologists do not know the mechanisms by which these drugs induce a leukemia, they believe they understand the underlying processes.

Direct damage to bone marrow and suppression of "immune surveillance" the protective process that prevents abnormal cells from persisting within the human body may be responsible. Up to 10 percent of patients with Hodgkin's disease who have been intensively treated with chemotherapeutic drugs or radiation therapy may ultimately display signs of an acute granulocytic leukemia. Specific antileukemia therapy can be used just as effectively in these patients as in previously healthy people. On balance, the benefit from the anticancer therapy in Hodgkin's disease greatly outweighs the risk of later developing a leukemia.

Organ transplant patients who receive drugs designed to suppress the immune system, which would otherwise reject the transplant, also have an increased incidence of cancers, including leukemia. Multiple myeloma, lymphoma, and other cancers of the lymph system also are associated with an increased risk of leukemia, probably because of the reduced immune function that accompanies these disorders. The division between "solid" tumors of the lymph system and the leukemias of the bloodstream is not completely distinct. Experience has shown that some lymphomas can have circulating cells in the bloodstream while the leukemias can sometimes form masses. A basic connection between the lymphomas and the leukemias has long been suspected, but its nature remains unknown.