Oncogene Expression and Arrangement in Human Leukemia

Abstract

It is generally assumed that human cancer results from a genetic mutation or series of mutations. There is a great deal of indirect evidence supporting this hypothesis. Studies with the X-linked G-6-PD marker indicate that most human malignancies are clonal (1) suggesting the occurrence of a rare event(s) in their development. Individuals with inherited defects in DNA repair such as Bloom’s syndrome and xeroderma pigmentosa are more susceptible to certain malignancies than normals (2). Most carcinogens or carcinogen metabolites are thought to act by binding to and altering DNA. Specific chromosome abnormalities are found in malignant cells but not in normal cells from patients with certain malignancies indicating the presence of specific genetic rearrangements in these particular cancers. However, until recently the specific genes effected by mutations producing cancer were completely unknown. This situation has changed remarkably in the past several years with the isolation and characterization of specific human genes (oncogenes) that may be intimately related to malignant transformation. Amplification, point mutations and chromosome rearrangements involving certain of these oncogenes have been described in various human malignancies including the leukemias.