Stem Cells, Vol 11, 9-19, Copyright © 1993 by AlphaMed Press
Chromosomal approaches to hematopoietic oncogenesis
PC Nowell
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6082.
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.
