Leukemia. Nature, types, and causes of leukemia

The term leukemia means “white blood” and arose from the discovery of extremely large numbers of white blood cells in the blood of certain persons; counts as high as 500,000 per cubic millimetre and even 1,000,000 per cubic millimetre may be found in some instances.

Leukemia is a potentially fatal disease of the blood-forming tissues that is encountered at all ages and in both sexes. There are two main varieties of leukemia, myelogenous, or granulocytic, and lymphatic. These terms refer to the types of cell that are involved. Each of these types is further subdivided into acute and chronic categories, and additional, less common varieties are recognized, as will be mentioned below.

Filterable viruses have been shown to cause leukemia in mice, rats, cats, and cows. These animal viruses are not infectious for human cells. A human retrovirus, human T-cell lymphotropic virus (HTLV-I), has been suggested to be the cause of a type of leukemia termedT-cell leukemia. Cases of T-cell leukemia associated with HTLV-I have been found in clusters in southern Japan (Kyushu) and in the coastal region of Georgia in the United States, but sporadic cases also have been identified. Other factors, such as ionizing irradiation, contribute to the development of leukemia. Ionizing irradiation is in fact a leukemia-inducing agent in humans. Survivors of the atomic bomb in Hiroshima and Nagasaki, pioneering radiologists who used inadequately shielded apparatus, and certain patients receiving a particular kind of irradiation are known to have developed leukemia with a frequency far exceeding that of the general population. Noteworthy is the fact that almost all radiation-induced leukemia has been of the granulocytic variety. The prolonged administration of radiomimetic drugs used in cancer chemotherapy, termed alkylating agents, is also associated with an increased risk of developing leukemia. Some evidence suggests that certain industrial chemicals, notably benzene, may cause leukemia. Genetic factors may lead to an increased frequency of leukemia in certain selected instances. This is suggested by evidence that shows the higher probability for acute leukemia occurring in bothidentical twins if one is affected as compared to both fraternal twins under the same conditions, and the frequency of development of acute myeloblastic leukemia in children with Down's syndrome, a condition in which there is a recognized chromosome defect. Evidence for the role of trauma, hormones, infections, and psychological and other influences as factors leading to the development of leukemia is unconvincing.

Advances in molecular genetics have greatly increased the understanding of leukemia. The disease seems to arise from a genetic change (mutation) in an early progenitor, or stem cell, in the bone marrow. The mutant cell passes the genetic change on to all of its progeny, thus giving rise to a clone of leukemic cells. In many cases of leukemia the mutation is detectable by analysis of the chromosomes of leukemic cells. A well-studied abnormality of this type, thePhiladelphia chromosome, occurs in almost all cases of chronic myelogenous leukemia. The chromosomal aberrations affect genes that influence vital aspects of cell growth and function. These genes, the oncogenes, may themselves be mutated or their regulation may be abnormal. The entire process, beginning with the mutation, usually involves many steps that culminate in a cell with the malignant attributes of a leukemic cell. This concept of the mechanism of leukemia has influenced treatment of the disease, which aims to eliminate the mutant clone and all of its progeny by chemotherapy or bone marrow transplantation (see below).