Chromosomal approaches to hematopoietic oncogenesis.

Abstract

Cytogenetic studies have provided an important approach to the identification of genes involved in the development of human leukemias and lymphomas and the "mutational" mechanisms leading to the altered function of these genes. Molecular dissection of chromosome translocations, in both lymphoid and myeloid tumors, has been particularly productive. Involvement of the c-myc gene has been demonstrated in both B cell and T cell tumors through association with an immunoglobulin or T cell receptor locus, respectively, and more than a dozen previously unknown "oncogenes" have been identified in other lymphoid tumor subgroups and are "activated" by a similar mechanism or by formation of a "fusion" gene with a locus on a different chromosome. In myeloid tumors, dissection of the translocation in Philadelphia chromosome positive leukemias has demonstrated involvement of the abl oncogene; other genes, both known and previously unknown, are beginning to be identified in translocations that characterize other classes of myeloid leukemia. These kinds of studies are being extended to search for tumor suppressor genes in association with chromosomal deletions, and some of the new molecular data are already being usefully applied in clinical diagnosis and management. Ultimately, there may also be specific therapies developed from these recent findings, but the recognition of how many different genes are involved has also indicated that no single, simple answer will be forthcoming.