CML develops when genetic material is exchanged between two of the 46 chromosomes that are in human cells, typically chromosomes 9 and 22, although in a small percentage of patients additional chromosomes are involved as well. The Philadelphia chromosome is the name for the abnormal chromosome 22. The scrambled genetic material on chromosome 22, called the bcr/abl fusion gene, directs the cell to produce a protein that triggers the growth of leukemia cells. Exactly how the bcr/abl fusion protein does this is not clear.
Staging
CML is divided into three phases according to the progression of the disease.
-
Chronic Phase
During this earliest stage of the disease, patients have a low number of blasts, or immature cells, within the bone marrow. In this phase blasts make up less than 5 percent of all bone marrow cells. Symptoms in the chronic phase are often mild. Most CML patients are diagnosed during this phase.
-
Accelerated Phase
In the accelerated phase, the number of blasts rises to between 5 and 19 percent of all bone marrow cells. Patients may develop symptoms including fever, weight loss, and a decrease in appetite because the spleen is enlarged.
-
Blast Phase
When the number of blasts increases to more than 20 percent of bone marrow cells, patients are considered to be in the blast phase, sometimes called a blast crisis. This phase of the disease is difficult to treat.
Doctors also distinguish among these phases of CML by determining if a patient has chromosomal abnormalities in addition to the Philadelphia chromosome. For example, if a patient has two Philadelphia chromosomes the disease is usually diagnosed as accelerated phase disease even if the blast count is less than 5 percent.
