CausesBy Mayo Clinic staff
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|How the Philadelphia chromosome forms|
Chronic myelogenous leukemia occurs when something goes awry in the genes of your blood cells. It's not clear what initially sets off this process, but doctors have discovered how it progresses into chronic myelogenous leukemia.
First, an abnormal chromosome develops
Human cells normally contain 23 pairs of chromosomes. These chromosomes hold the DNA that contains the instructions (genes) that control the cells in your body. In people with chronic myelogenous leukemia, the chromosomes in the blood cells swap sections with each other. A section of chromosome 9 switches places with a section of chromosome 22, creating an extra-short chromosome 22 and an extra-long chromosome 9.
The extra-short chromosome 22 is called the Philadelphia chromosome, named for the city where it was discovered. The Philadelphia chromosome is present in the blood cells of 90 percent of people with chronic myelogenous leukemia.
Second, the abnormal chromosome creates a new gene
The Philadelphia chromosome creates a new gene. Genes from chromosome 9 combine with genes from chromosome 22 to create a new gene called BCR-ABL. The BCR-ABL gene contains instructions that tell the abnormal blood cell to produce too much of a protein called tyrosine kinase. Tyrosine kinase promotes cancer by allowing certain blood cells to grow out of control.
Third, the new gene allows too many diseased blood cells
Your blood cells originate in the bone marrow, a spongy material inside your bones. When your bone marrow functions normally, it produces immature cells (blood stem cells) in a controlled way. These cells then mature and specialize into the various types of blood cells that circulate in your body — red cells, white cells and platelets.
In chronic myelogenous leukemia, this process doesn't work properly. The tyrosine kinase caused by the BCR-ABL gene causes too many white blood cells. Most or all of these contain the abnormal Philadelphia chromosome. The diseased white blood cells don't grow and die like normal cells. The diseased white blood cells build up in huge numbers, crowding out healthy blood cells and damaging the bone marrow.
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