Chronic myelogenous leukemia, or CML, is a type of slow-progressing cancer of the white blood cells. CML starts in the bone marrow where white blood cells are produced. White blood cells are part of the immune system and help to fight off infection.
CML is almost always associated with a chromosomal abnormality called the Philadelphia chromosome. The Philadelphia chromosome produces a gene called BCR-ABL which, in turn, produces a protein that causes too many stem cells to develop into white blood cells. Unlike other blood cells, these new, diseased white blood cells don't die off, instead they accumulate in the body. Eventually these diseased cells crowd out other healthy blood cells and damage the bone marrow, spleen, liver and blood, and then spread to other parts of the body.
CML is highly treatable when detected in the first phase of the disease, call the chronic phase. There is no cure for CML. But targeted therapy drugs such as imatinib (Gleevec), dasatinib (Sprycel) and nilotinib (Tasigna) are highly successful in putting the disease into remission for an indefinite period of time.
What causes CML?
CML occurs when something goes wrong in the genes of the blood cells, but doctors aren't sure what initially triggers CML to develop. About 90 percent of patients with CML have developed an abnormal chromosome in their blood cells called the Philadelphia chromosome. Doctors aren't sure what causes this abnormal chromosome.
"This chromosomal abnormality probably happens in people all the time and is recognized as an abnormality and deleted," says Matt Kalaycio, MD, director of the Chronic Leukemia and Myeloma Program at the Cleveland Clinic. "But for whatever reason, in some people, it happens and it stays."
High doses of radiation, such as those from cancer treatment, may lead to the development of CML. However, most people who receive radiation treatment for cancer do not develop CML and most people with CML have not been exposed to high doses of radiation. Dental and medical x-rays have not been linked to CML.
What is the Philadelphia chromosome?
Named after the city in which it was discovered, the Philadelphia chromosome is a chromosome that develops because of an abnormality in the cells. It is formed when a section of chromosome 9 switches places with a section of chromosome 22, creating an extra-long chromosome 9 and an extra-short chromosome 22. The extra-long chromosome 22 is the Philadelphia chromosome.
The Philadelphia chromosome produces a new gene called BCR-ABL (BCR comes from the original chromosome 22 and ABL comes from the original chromosome 9). The BCR-ABL gene instructs the blood cells to produce too much of a certain enzyme called tyrosine kinase. Tyrosine kinase causes blood stem cells (which are different from embryonic stem cells) to produce too many white blood cells. These new white blood cells are not like normal cells in that they grow out of control and do not die as they should. This crowds out healthy blood cells, leading to damage to the bone marrow. Eventually the diseased blood cells infect other areas of the body.
Is CML hereditary?
No, CML is not hereditary, meaning it cannot be passed from parent to child. The Philadelphia chromosome is limited to cells in the blood. "Blood cells are not passed from mother to fetus," says Dr. Kalaycio.
How common is the disease?
CML is rare, affecting one to two out of every 100,000 people, most often middle-aged adults, and makes up 7 - 20 percent of total leukemia cases. CML rarely occurs in children. The National Cancer Institute estimated that just over 5,000 new cases of CML were diagnosed in 2009, and that approximately 22,500 people are living with CML in the United States.
Why is CML more common in adults than children?
Though scientists aren't exactly sure, time, in terms of advanced age, probably explains why CML occurs more often in adults than children. Because CML is caused by a chromosomal abnormality, the probability that an abnormality will occur increases each time the genes replicate, explains Dr. Kalaycio. An adult's genes have replicated millions of more times than a child's genes and therefore have a higher likelihood of developing the abnormality.