Genetic Consequences of Chromosomal Translocations

The malignant cells in many patients who have leukemia, lymphoma, or another hematologic neoplasm have acquired clonal chromosomal abnormalities. Specific cytogenetic abnormalities are closely, and sometimes uniquely, associated with morphologically and clinically distinct subsets of leukemia or lymphoma (1,2). The detection of a cytogenetic abnormality clearly distinguishes between benign reactive lymphoid or myeloid hyperplasia and a malignant proliferation (1). Moreover, the detection of recurring cytogenetic abnormalities may predict the clinical course, and the likelihood of responding to particular treatments, for example, retinoic acid (RA) in acute promyelocytic leukemia (APL) (3–5). In many cases, the prognostic information derived from cytogenetic analysis is independent of that provided by other clinical features. Patients with favorable prognostic features may be treated with standard regimens, whereas those with less favorable clinical or cytogenetic characteristics may be better treated with more intensive or investigational therapies (3–5). In addition, the disappearance of a chromosomal abnormality, or an abnormal clone, that was present at diagnosis is an important indicator of complete remission following treatment, and its reappearance invariably heralds relapse of the disease. This chapter focuses on the genetics of the leukemias and lymphomas from primarily a cytogenetic perspective.