Familial leukemia

Identification of genes responsible for rare familial cases of cancer provides genetic and biochemical insight into the mechanisms of carcinogenesis at work in the more common, sporadic occurrences of the corresponding malignancy. Hematopoietic malignancy is no exception, and considerable evidence substantiates the role of genetic factors in the risk for leukemia. In a few instances, leukemia runs in families as a single gene, Mendelian disorder. Only a few genes conferring heritable risk for leukemia are known, however, and most are responsible for bone marrow failure syndromes. Thus, the identification of additional genetic risk factors for leukemia represents both a challenge and an opportunity. The high frequency of leukemia and transient leukemia in Down syndrome is beginning to yield the secrets of its unique clinical properties. The apparent phenomenon of anticipation (a declining of age of onset with each passing generation) in familial forms of bone marrow failure and leukemia is now affirmed through its association with mutations in genes responsible for maintaining telomere length. And, for the majority of leukemia cases, as with other common diseases that are not under the influence of a single, major gene, but rather result from the additive interactions of complex genetic and environmental factors, common variants in metabolic enzymes, and other genes awaiting discovery, are being teased out.