Biomedical Engineering Reference
In-Depth Information
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7. 1 4
Karyotype of a male with the Philadelphia chromosome. The
two arrows point to the chromosomes that contain the translocation
(photograph courtesy of Lisa Osborne of the Institute of Genomic
Medicine, UMDNJ-New Jersey Medical School).
changes evolve, some removing tumor suppressor genes and others activat-
ing other oncogenes - eventually resulting in the change from the chronic
to the acute stage of the disease.
Researchers focusing on the fusion gene's protein product discov-
ered that it created an abnormal tyrosine kinase activity that led to
CML. One of the critical steps in this enzyme's action is the binding of
adenosine-5′-triphosphate (ATP) to a site on the fusion bcr-abl protein,
which starts a cascade of events leading to the leukemia. Armed with this
knowledge and some detailed information about this active ATP site, phar-
maceutical companies launched an effort to discover a drug that would
competitively bind to the ATP site and block this reaction. Their efforts
resulted in a drug called Gleevec, which is successful in producing remission
in the vast majority of CML patients.
Numerous other chromosome markers are associated with various neo-
plastic pre-cancerous states, and these markers have become essential in the
diagnosis, prognosis and staging of these disorders. Molecular studies have
shown that these chromosome changes are not random occurrences, but are
relatively specifi c to the cancer involved and that they generally cause the
activation of oncogenes and/or the removal of tumor suppressor genes.
Recently there have been discoveries that have correlated genetic syn-
dromes with small deletions of specifi c chromosome areas. These disorders
