About 4,400 new cases of chronic myelogenous leukemia (CML) are diagnosed each year in the United States. Chronic myelogenous leukemia may be called by several names, including chronic granulocytic, chronic myelocytic or chronic myeloid leukemia.
CML results from an acquired (not inherited) injury to the DNA of a stem cell in the marrow. This injury is not present at birth. Scientists do not yet understand what produces this change in the DNA in patients with CML. This change in the stem cell's DNA confers a growth and survival advantage on the malignant stem cell. The result of this injury is the uncontrolled growth of white cells leading, if unchecked, to a massive increase in their concentration in the blood. Unlike acute myelogenous leukemia (AML), chronic myelogenous leukemia permits the development of mature white blood cells that generally can function normally. This important distinction from acute leukemia accounts for the less severe early course of the disease.
Most cases of chronic myelogenous leukemia occur in adults, but children may develop the disease. Chronic myelogenous leukemia accounts for about 4 percent of childhood leukemia cases. Childhood cases (under 20 years of age) represent about 2 percent of all patients who develop chronic myelogenous leukemia. The frequency of the disease increases with age from about one in 1 million children in the first 10 years of life to one in 100,000 people at age 50, to one in 10,000 people at age 80 and above. The disease in children is similar in behavior to that of adults; however, the outcome of stem cell transplantation is better in younger individuals.
Chronic myelogenous leukemia is distinguished from other leukemias by the presence of a genetic abnormality in blood cells, called the Philadelphia chromosome. The changes that result in this chromosome "causing" chronic myelogenous leukemia have been studied intensively. In 1960, two physicians studying chromosomes in cancer cells noticed that a chromosome in CML patients was shorter in length than that of the same chromosome in normal cells. They named this shortened chromosome the Philadelphia chromosome, because the observation was made at the University of Pennsylvania School of Medicine in that city.
The total of 46 chromosomes in normal human cells is composed of 22 pairs of chromosomes numbered 1 to 22 and two sex chromosomes (either an X and Y in males or two X's in females).
The Philadelphia chromosome (No. 22), which is an abnormally short chromosome, is usually referred to as the Ph-chromosome.
Further studies established that two chromosomes, usually chromosome Nos. 9 and 22, were abnormal. Pieces of the chromosomes, which are broken off in the blood cells of patients with chronic myelogenous leukemia, switch with each other. The detached portion of chromosome 9 sticks to the broken end of chromosome 22, and the detached portion of chromosome 22 sticks to the broken end of chromosome 9. This abnormal exchange of parts of chromosomes is called a translocation. This translocation of chromosome pieces occurs only in the stem cell and in the various blood cells derived from that stem cell. The chromosomes of the cells in other tissues are normal.
The cause of the chromosomal breakage in virtually all CML patients is not known. In a small proportion of patients, the cause of the breakage is exposure to very high doses of radiation. This effect has been most carefully studied in the Japanese survivors of the atomic bomb, whose leukemia risk was significantly increased. A slight increase in risk also occurs in some individuals treated with high dose radiotherapy for other cancers, such as lymphoma. Exposures to diagnostic dental or medical x-rays have not been associated with a heightened risk of chronic myelogenous leukemia.
The onset of chronic myelogenous leukemia is associated with symptoms that usually develop gradually. Most patients feel a loss of well-being. They tire more easily and may feel short of breath when physically active. They may have a pale complexion from anemia. Discomfort on the left side of the abdomen from an enlarged spleen is a frequent complaint. Patients may experience excessive sweating, weight loss and inability to tolerate warm temperatures. Increasingly, the disease is discovered during the course of a "routine" medical examination. Since the disease worsens over weeks or months, most patients would have symptoms develop soon after such a medical examination in any case.
To diagnose the disease, the blood and, in most cases, the marrow cells must be examined. The white cell count invariably increases, often to very high levels. Examination of the stained (dyed) blood cells with a light microscope shows a characteristic pattern of white cells: a small proportion of very immature cells (leukemic blast cells), and a larger proportion of maturing and fully-matured white cells (myelocytes and neutrophils).
Courtesy of the Leukemia and Lymphoma Society.