Chronic Myelogenous Leukemia (CML)
Chronic myelogenous leukemia occurs when, in the bone marrow, an early form of a white blood cell suffers a genetic defect. The cell fails to go through a normal life cycle and multiplies, leading to an overload of white blood cells in the bone marrow.
The affected cells are from the myeloid cell line, in particular the neutrophils. In early stages of the disease, the abnormal cells may mature correctly and carry out their usual disease-fighting functions. Later on, they will lose their ability to mature and work properly. The immature cells are called blasts or leukemic blasts.
People who have CML have a chromosome abnormality -- the Philadelphia chromosome -- in their stem cells and blood cells. The abnormality is a translocation, in which two chromosomes swap pieces of genetic material. In the case of CML, chromosome 22 has exchanged material with chromosome 9. The altered genetic material now found on chromosome 22, which includes pieces from both chromosomes, is called the BCR-ABL fusion gene. It tells the body to produce a protein that somehow triggers the growth of leukemic cells. This same gene is also somehow activated in other CML patients whose chromosomes have not undergone such a translocation.
Those who have the Philadelphia chromosome may be diagnosed as Ph1-positive, while others are considered Ph1-negative.
CML generally progresses more slowly than acute forms of myelogenous leukemia. Some patients will remain in a fairly stable chronic phase of the disease for several years.
CML is also known as chronic granulocytic leukemia.
Symptoms
CML can develop very slowly, causing no noticeable symptoms in early stages. Many people have no symptoms at all when first diagnosed; the condition is found in the course of a routine physical examination, when blood tests reveal an abnormally high number of white blood cells.
As the disease progresses, the person may feel fatigued or just "not well." He or she may be short of breath, may lose weight, and may develop a feeling of fullness in the abdomen. Other common symptoms are bone and joint pain, paleness, sweating, fever, pain in the upper left abdomen, and bleeding problems.
Who Gets CML
Chronic myelogenous leukemia is found primarily in adults. The average age at onset is between 40 and 50, and it is slightly more common in men. Children can also develop the disease, but it is very uncommon.
Risk Factors
Known risk factors for CML include exposure to very high doses of radiation. There is also a slightly higher risk among people who received high-dose radiation as treatment for cancer.
Risk factors, however, account for only a small percentage cases of CML; most people who develop the disease have no risk factors. And even if risk factors are present in one's history, it is rarely possible to say exactly what caused one person's leukemia.
Stages of CML
CML is divided into three phases.
- Chronic phase. This is the earliest stage of the disease. Patients have a very low proportion of immature cells or blasts in their blood -- generally under 5 percent of all blood cells. Symptoms are mild or nonexistent. Patients may remain in this phase for months or years. Most people are diagnosed while in this phase.
- Accelerated phase. This phase occurs when blasts have risen to between 5 and 30 percent of blood cells. Symptoms include fever, weight loss, and a loss of appetite.
- Blast phase. This phase is defined as when blasts account for more than 30 percent of all blood cells. The blasts often have moved out of the bone marrow and into other tissues and may collect and form tumors in the lymph nodes or bones. At this point the disease is considered an aggressive acute leukemia. This phase is sometimes called a blast crisis or the acute phase.
Prognostic Factors
Factors that can indicate a less favorable outcome for patients with CML include an enlarged spleen, being in the later phases of the disease, having abnormal platelet counts, and being over the age of 60.
