Chronic Myeloid Leukemia impacts approximately 5000 people a year. It is characterized by the uncontrolled growth of a subset of circulating white blood cells (WBC). The onset of this disease correlates with a particular genetic abnormality that has been well categorized. The change in the genetic material is demonstrated by the appearance of the so-called “Philadelphia” chromosome. This chromosome results from the anomalous exchange of genes between chromosome 9 and chromosome 22 – the human genome possesses 23 pairs of chromosomes one pair of which contains the genes that determine human gender XX (female) and XY (male). This genetic rearrangement results in the juxtaposition of two genes namely, BCR and ABL. The resulting gene combination, BCR-ABL is responsible for the production of a novel gene product that contributes to uncontrolled cell growth i.e. CML.
The realization of this mechanism opened the possibility that if the activity of the deleterious protein product could be curtailed, a cure of CML could be envisioned. This particular approach is known as molecular targeting, for it targets a particular molecular substance known to play a critical role in the development of disease – in this case, CML.
When it became clear that the “offending” protein was a member of a class of proteins referred to as kinase enzymes, Drs. Zimmerman and Buchdunger tested a plethora of possible drug candidates to see what compound could precisely target this enzyme without adversely affecting any other cellular processes. Their work proved rewarding; they ultimately discovered the efficacy of a drug given the name, Gleevec (imatinib).
The results have been very impressive. As reported in the Journal of the National Cancer Institute (JNCI), CML patients who have been treated with Gleevec have gone into complete remission after two years of treatment and have been shown to have survival rates similar to the general population. According to a statement released by the journal, “This study offers the first evidence that a disseminated cancer, not amenable to surgery, can be controlled to the point of giving patients a normal life expectancy.”
These results are extraordinary, yet they point to the efficacy of the molecular targeting approach. This methodology may prove applicable to other heretofore treatment-resistant diseases.