5. Science and Technology for Disease Control: Past, Present, and Future

1960 An abnormal chromosome, named the Philadelphia chromosome, was found in the white cells of most patients with chronic myeloid leukemia (CML).

1973 By the use of specific dyes to label chromosomes, notably quinocrine fluorescence and Giemsa staining, the Philadelphia chromosome was found to be the result of a translocation between chromosomes 9 and 22: t(9:22)(q34:q11).

1983 It was found that the translocation that causes the Philadelphia chromosome juxtaposes the c-abl oncogene from chromosome 9 with a breakpoint cluster (bcr) region on chromosome 22, resulting in an abnormal bcr/abl gene. The product of this gene, an abnormal tyrosine kinase, has increased tyrosine kinase activity compared with the product of the normal c-abl gene, a major fact in causing the uncontrolled white cell proliferation characteristic of CML.

1996 A selective inhibitor of the abnormal tyrosine kinase produced by the bcr/abl gene product was developed that results in a high remission rate in patients with CML and other tumors.

A major advance in the understanding of the mechanisms of malignant transformation followed the discovery that many forms of cancer result from the acquisition of mutations in cellular oncogenes—that is, normal housekeeping genes of cells that are involved in a variety of regulatory functions. In some cases, we may be born with a mutation of this kind, but the vast majority of cancers seem to be attributable to acquired mutations involving one or more oncogenes. The discovery of a drug that was able to interfere specifically with the activity of the product of an abnormal oncogene was a major advance in oncology, offering the hope that future research will make it possible to tailor-make agents directed at abnormal oncogene activity for the treatment of cancer.

Source: Bartram and others 1983; Druker and others 1996; Klein and others 1982; Nowell and Hungerford 1960; Rowley 1973.