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Nearly all cases of chronic myeloid leukemia (CML) are caused by a swapping of genetic material between chromosomes within the cells that results in a shorter version of chromosome 22, known as the Philadelphia (Ph) chromosome. This chromosome contains an abnormal gene, known as BCR-ABL, that causes the leukemia cells to continue to grow and divide.
Doctors can use the fact that CML cells contain the Philadelphia chromosome (and the BCR-ABL gene) to diagnose CML by looking for these abnormalities in a sample of a patient's blood or bone marrow. If CML has already been diagnosed, doctors can also look for the Philadelphia chromosome (or the BCR-ABL gene) in blood or bone marrow samples during treatment to see how well it is working. These abnormalities should go away if the treatment is effective.
Several kinds of lab tests can be used to look for the genetic changes that indicate CML cells:
Cytogenetics. In this test, the chromosomes inside a cell are stained with special dyes and looked at under a microscope. Major abnormalities in the chromosomes (such as the presence of the Philadelphia chromosome) can often be seen with this test, but smaller chromosome changes may not be visible. The cells must be grown in the lab for the chromosomes to be seen, which may take a week or more. Because of this and the fact that not all chromosome changes may be seen, other lab tests may be done.
Fluorescence in situ hybridization (FISH). This test is another way to look for changes in chromosomes. The cells in the sample are stained with special fluorescent dyes that will only attach to certain parts of chromosomes (such as parts of the BCR-ABL gene, if it is present). The cells are then viewed under a microscope using a special light. This test can find some chromosome changes that can't be seen with standard cytogenetic testing. It is also a quicker test. Many medical centers now use this test.
Polymerase chain reaction (PCR). This is a very sensitive test that can detect extremely low levels of the BCR-ABL gene in a test sample. It works by amplifying the amount of genetic material in a sample so that it can be detected. This test is capable of finding small levels of a gene even when other tests can't find it.
During treatment for CML, monitoring a patient's blood and bone marrow for CML cells (using standard blood tests and the lab tests above) is very important. If cells containing the Ph chromosome can't be detected with standard lab tests, the PCR test may be done to see if small amounts of the BCR-ABL gene can still be found.
The main goal of treatment is to reduce or remove cells with the Ph chromosome to eliminate symptoms and achieve remission. Doctors may watch for 3 types of responses to treatment:
Hematologic response. A return of blood cell counts to normal, with no CML cells seen in the blood, and the spleen is a normal size. This type of response usually occurs within a couple of months of starting treatment for chronic phase CML.
Cytogenetic response. A change in the amount of cells with the Ph chromosome in the blood or bone marrow. There are different levels of cytogenetic response:
Minor cytogenetic response. A lowering of the number of cells with the Ph chromosome in the blood or bone marrow, though they are still found in 35% to 90% of the cells.
Major cytogenetic response. This is when the percentage of cells with the Ph chromosome drops to 35% or less than that seen at diagnosis. This term is sometimes used to describe either a complete or partial response.
Complete cytogenetic response. This is when the Ph chromosome is no longer found in the blood or bone marrow by cytogenetic or FISH testing.
Partial cytogenetic response. This is when less than 35% of the cells still have the Ph chromosome.
Molecular response. This is based on the results of PCR testing and is 1 of 2 types:
Complete if the BCR-ABL gene can't be detected
Major if the level of BCR-ABL detected is very low
Studies have shown that people with CML who have a complete or partial cytogenetic response tend to live longer than those who do not. However, the leukemia may still come back in some people after achieving a complete cytogenetic response. This may be less likely after stem cell transplantation.
During treatment, the doctor generally checks your blood and bone marrow cells every 3 to 6 months to see whether the treatment is destroying leukemia cells. If 1 type of treatment has no effect, or if it works for a while and then stops, doctors want to know as soon as possible so that they can switch to another type of treatment.
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