Doctors believe CML starts when a genetic mistake or mutation occurs in a single hemopoietic stem cell. What causes this mutation is unknown, and probably differs for different people. Doctors report an increase in CML and other leukemias following the nuclear bombings of Japan during World War II, so there may be some correlation between high levels of radiation and the development of CML. In very rare instances, doctors believe there may be a slight genetic predisposition to CML.
The Philadelphia Chromosome
While the specific trigger for CML is unknown, doctors understand much of the process by which the disease unfolds. In the vast majority of cases of CML, the disease starts when two chromosomes swap parts during cell division. This is called a translocation. One of the abnormal chromosomes that results is called the Philadelphia chromosome, and this is the distinguishing feature in most cases of CML.
The Philadelphia chromosome contains a unique gene called BCR-ABL which produces an abnormal enzyme, also referred to as BCR-ABL. The abnormal BCR-ABL enzyme interferes with the programmed life cycle of white blood cells. In CML, white blood cells do not die as they normally should. This, and other mechanisms that are only partially understood, leads to the over-production and accumulation of these blood cells.
