Chronic Myeloid Leukemia and the Development of Gleevec
Why is the story of the development of Gleevec important?
The development of this drug has been particularly satisfying intellectually, with direct benefits for patient care arising from several decades of basic science research. Furthermore, the story of this drug illustrates the promises of the human genome project and reflects the vast investment made in the basic science of human biology over the past four decades. The human genome project is a monumental international effort to identify all of the genetic information in the human chromosomes.
What were the early findings in the development of Gleevec?
The Philadelphia chromosome was first recognized as a shortened chromosome 22. (Chromosomes are thread-like structures in every cell nucleus. 23 pairs of chromosomes carry all of an individual's genes. The genes, in turn, carry the codes to produce the proteins that determine all of an individual's characteristics.) Anyhow, this chromosomal shortening was noted in 90% of patients with chronic myeloid leukemia. What's more, this abnormality was only found in the malignant (cancerous) cells, while the nonmalignant cells in the patients did not have the abnormality. Hence, this was the first consistently noted chromosomal abnormality that was associated with a malignancy. As a matter of fact, these observations led directly to the prevailing theory that most malignancies are the result of acquired genetic mutations (alterations of the genes).
To continue with the chromosome 22 part of the story: Subsequently, it was noted that the missing piece of chromosome 22 had in fact attached itself (translocated) to chromosome 9, while a portion of chromosome 9 had translocated to chromosome 22. Furthermore, it was found that the breakage on chromosome 22 consistently occurred (that is, clustered) in the same narrow region of the chromosome. This region, therefore, became known as the breakpoint cluster region, or BCR for short. During the time that these biological observations on the shortened chromosome 22 were being made, not much change was occurring in the treatment of chronic myeloid leukemia. Basically, the treatment at that time revolved around controlling the high white blood cell counts by using an agent named busulfan (Myleran).
What is chronic myeloid leukemia and how has it been treated?
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