Chronic myelogenous leukemia is characterized by an initial slowgrowing phase, followed three to five years later by an aggressive and uniformly lethal phase (if not treated).
Fortunately, we know more about CML than about any other cancer. In fact, CML is a disease of firsts. It was the first disease to be labeled “leukaemia,” in 1845 by the famous German pathologist Rudolf Virchow, who described several patientswith elevated levels of “colorless corpuscles” (representing white blood cells) and enlarged spleens.
In what marks a turning point in cancer research, CML was the first cancer to be associated with a specific chromosomal abnormality, termed the Philadelphia chromosome, after the city in which the discovery was made; this established, for the first time, that cancer is marked by alterations to DNA. Most recently, CML came to be the first cancer to be treated with startling success by a new wave of cancer treatments called targeted therapies.
CML arises when a bone marrow stem cell experiences a genetic mutation that results in the exchange of genetic material between two chromosomes. As a result, a gene called Bcr becomes joined to another gene called Abl. The resulting Bcr/Abl fusion gene gives rise to a powerful mutant protein that makes the cell grow faster, resist cell death, and acquire the characteristics of a leukemia cell. Bcr/Abl is essential for the development of CML; the discovery of ways to inhibit its function has revolutionized the treatment of this disease.
For many years the only hope for cure of CML was a bone marrow transplant from another person. In 1999 a drug called imatinib (Gleevec) was approved by the FDA based on extremely positive results in the first stages of testing. Gleevec is a pill that is well tolerated by patients and specifically shuts down the action of Bcr/Abl. CML cells die when Bcr/Abl stops functioning, and many patients achieve a complete remission of their disease.
It is too early to tell if Gleevec is curing CML permanently, but the drug has enabled many patients to delay, if not completely avoid, the need for bone marrow transplantation. Remarkably, for those patients in whom CML grows after an initial response to Gleevec, new drugs such as dasatinib (Sprycel) and nilotinib (Tasigna) are effective in reestablishing remission in many cases. It is hoped that CML will remain a disease of firsts and become the first leukemia to be cured by medicines that work with pinpoint accuracy rather than with intensive chemotherapy or transplantation.
