BCR-ABL Testing for Imatinib (Gleevec®) Response

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BCR-ABL Testing for Imatinib (Gleevec®) Response

What Is BCR-ABL?

BCR-ABL is an abnormal gene found in most people with chronic myelogenous leukemia (CML) and in some people with acute lymphoblastic leukemia (ALL). The BCR-ABL gene is created when two different genes join together that normally aren't connected. Monitoring how active the BCR-ABL gene is can tell you if certain treatments are working to control your leukemia.

BCR-ABL and the Philadelphia Chromosome

People have 23 pairs of chromosomes in each cell of their body. Normally, the ABL gene is located on chromosome number 9. The BCR gene is located on chromosome 22. The BCR-ABL gene is created when chromosome 9 and chromosome 22 accidentally exchange part of their DNA and become joined together. When chromosomes exchange DNA, it's called a translocation. The translocation that joins BCR-ABL can usually be seen under a microscope. It is sometimes called the "Philadelphia (Ph) chromosome."

When the BCR and ABL genes are joined, they create a new gene that makes an abnormal protein. The abnormal protein, called a tyrosine kinase, causes white blood cells in the bone marrow to grow and reproduce out of control. They crowd out the normal cells in the bone marrow and this leads to cancer.

The presence of a Ph chromosome is enough to confirm a diagnosis of CML and ALL. If you are currently being evaluated for either of these types of cancer, your doctor will want to test your blood or bone marrow to confirm the presence of the Ph chromosome.

  • Almost all people with CML have a Philadelphia chromosome that joins BCR and ABL. A few people with CML (around 5%) have BCR joined to ABL in another way — they don't have a chromosome translocation that can be seen by microscope.
  • About 1 in 4 people with ALL have a Philadelphia chromosome. This is called "Ph+ ALL".

Once a diagnosis is confirmed, your doctor will probably order BCR-ABL testing to establish baseline BCR-ABL activity levels.

Doctors don't know why a Philadelphia chromosome happens in some people and not others. Although the Philadelphia chromosome is a genetic change, it is not inherited and can't be passed down from parent to child.

BCR-ABL and Monitoring Treatment Response

Once a Philadelphia chromosome is diagnosed in someone with CML or ALL, the first treatment is usually a drug called imatinib (Gleevec®). Imatinib is a "targeted" therapy that directly blocks the specific protein that is made by the BCR-ABL gene. This leads to lower numbers of abnormal white blood cells so healthy cells can survive.

Imatinib is very effective and has been shown repeatedly to work better for most people than older medications like interferon. About two-thirds of people with CML responded well to imatinib within 12 months of treatment. After 5 years of treatment almost 90% of people with CML had reduced BCR-ABL activity. A few people, about 5% to10%, don't respond to imatinib or become resistant to it. These people can take dasatinib (Sprycel®) or nilotinib (Tasigna®), which are similar drugs. This group of drugs are called tyrosine kinase inhibitors.

People taking imatinib need periodic testing to monitor how well the drug is working. There are several tests available. The information provided on this site focuses on measuring how active the BCR-ABL gene is.

Next: Who Should Consider BCR-ABL Testing?