Genetic tests on your chronic myeloid leukaemia (CML) cells
You have tests on your blood and bone marrow to look for changes in certain 
. This helps:
- diagnose your type of leukaemia
- learn more about your CML cells
- the doctors see how well your treatment is working
The tests on the cells look for 2 changes in particular:
- the Philadelphia chromosome
- the BCR-ABL gene
You might see the BCR-ABL1 gene written in a more scientific way BCR::ABL1.
Genetic tests are also done to look for other abnormal .
You might hear these tests called cytogenetic tests, chromosomal analysis or molecular analysis. The doctors are looking for changes in genes and chromosomes in the leukaemia cells.
These genetic tests on your leukaemia cells should not be confused with tests that look for inherited gene changes. These gene changes are only found in the blood cells and happen during your lifetime. It is not something you were born with so it is not something that can be passed on to your children.
Why you might have these tests
The results of these tests:
- help doctors diagnose your leukaemia
- check how well your treatment is working
- provide information about how your CML might behave – this helps your doctor talk to you about your outlook (prognosis)
You usually have these tests at diagnosis. And then at regular intervals during your treatment.
What are genes and chromosomes?
Most body cells contain chromosomes. Chromosomes are made up of thousands of genes. There are 23 pairs of chromosomes in most human cells. Each chromosome has a number from 1 to 23. These are a bit like an instruction manual for building the body and keeping it healthy.
Sometimes a change happens in the genes when a cell divides. This happens by chance. It is not something you inherit. So you were not born with it and it can't be passed on to your children.
CML develops when an abnormal change happens to chromosome 9 and chromosome 22.
Understanding your results
The BCR-ABL1 gene
The BCR-ABL1 gene is made when a piece of one chromosome breaks off and attaches to another. This process is called translocation.
On chromosome 9 there is a gene called the ABL1 gene. And on chromosome 22 there is a gene called BCR. A completely new gene called BCR-ABL1 is made when the ABL1 gene breaks off and sticks to the BCR gene. The BCR-ABL1 gene is known as a fusion gene. This is because 2 genes that should be separate are stuck together (fused).
The BCR-ABL1 gene causes the cell to make too much of a protein called tyrosine kinase. This protein encourages leukaemia cells to grow and multiply. The main treatment for CML are drugs called tyrosine kinase inhibitors (TKIs). These drugs work by blocking (inhibiting) the chemical messengers that the BCR-ABL1 gene makes.
All people with CML have the BCR-ABL1 fusion gene.
The Philadelphia chromosome
The translocation process changes chromosome 22. This is now called the Philadelphia chromosome.
Most people with CML have the Philadelphia chromosome. Occasionally some people might not have it. This is because of how some of the chromosomes have stuck together.
Scientists can see the Philadelphia chromosome when they look at blood and bone marrow under the microscope. So they use it to help diagnose CML and to monitor response to treatment.
Watch this 2 minute video to explain what Philadelphia positive leukaemia is.
The human body is made up of trillions of cells. Inside each cell is a nucleus and within the nucleus are the cell’s chromosomes. There are 23 pairs in total.
Chromosomes are made up of DNA, which gives the instructions that tell a cell what to do. Sections of DNA are called genes. They carry the information that makes you you. For example, they tell your body what colour your hair will be or what colour your eyes will be.
Genes also tell your cells when to divide and grow, and when to die.
When cells divide to make new cells, they make exact copies of the chromosomes.
In Philadelphia chromosome positive leukaemia an abnormal change happens to chromosomes 9 and 22. Part of chromosome 9 breaks off where the gene ABL1 is located and part of chromosome 22 breaks off where the BCR gene is located. The broken parts swap places creating a new gene on chromosome 22.
This new chromosome is called the Philadelphia chromosome and the new gene is called BCR-ABL1. This new gene tells the cell to make a large quantity of a protein called tyrosine kinase which encourages leukaemia cells to grow.
There are targeted cancer drugs that can block the protein and stop the leukaemia from growing. These drugs are called tyrosine kinase blockers. You take them as tablets.
For more information about your type of leukaemia and treatments go to CRUK.org/about-cancer/leukaemia.
Types of tests
There are different types of tests.
FISH tests
FISH stands for fluorescence in situ hybridisation. This is usually the first test that you have. It is quite a quick genetic test compared to others.
The FISH technique uses a fluorescent dye that glows up under a special microscope. This makes it easier to see particular gene and chromosome changes. Doctors use the FISH test to look for the BCR-ABL1 gene on the chromosomes. All people with CML have the BCR-ABL1 gene.
For this test scientists label specfic genes with a green and red dye. In this case they label the BCR gene and ABL1 gene. When these 2 genes join they make the BCR-ABL1 gene. Under the microscope this is picked up as the join turns yellow.
This test can be useful if the doctors haven’t seen the Philadelphia chromosome in your cytogenetic test, but they still think you might have CML.
Doctors can also use FISH tests alongside other tests to help assess your response to treatment.
Cytogenetic tests
This is a standard (conventional) test that doctors use to look at chromosomes. It's also called karyotyping or G-banding. It is when scientists use a microscope to look at the chromosomes in your blood and bone marrow. They look at the size, shape and number of chromosomes.
The best time to see chromosomes is when the cell is dividing. So the scientists have to grow a sample of blood or bone marrow in the laboratory. Then they look at the sample when the cells start to divide. It can take some time to get the results of this type of test.
The scientists are looking for the Philadelphia chromosome. They also look for other changes. This is known as additional chromosomal abnormalities (ACA).
You usually have cytogenetic analysis to help diagnose your CML. You might then have this test to see how well treatment is working.
Polymerase chain reaction (PCR) tests
This test looks for genetic changes in the blood or bone marrow cells. Doctors use it to look for the BCR-ABL1 gene. It is a very sensitive test, which can detect tiny amounts of the BCR-ALB1 gene. So it is a very useful test for monitoring CML.
Doctors like to use this test to monitor CML because:
- they don’t need to grow the cells first, so it can be quicker test than cytogenetic analysis
- it is much more sensitive than karyotyping and FISH tests
- they can do the test on a blood sample which is easier to take than a bone marrow sample
PCR tests can measure how much BCR-ALB1 is there. It is the most useful test to check how well treatment is working. You have this test at diagnosis and then at regular intervals during your treatment.
Sometimes scientists can adapt the PCR test to look for changes within the BCR-ABL1 gene. Cancer drugs called tyrosine kinase inhibitors (TKI) are a common treatment for CML. Looking for particular changes can be useful if you are not responding to a certain tyrosine kinase inhibitor. It can also help doctors select the right type of TKI for your leukaemia.
What happens
The doctor can do these tests on:
- a blood sample
- a bone marrow sample
You have blood tests at diagnosis and regular blood tests during treatment.
You may have a bone marrow test at diagnosis. You sometimes need bone marrow tests during treatment. Your doctor will discuss this with you.
How do doctors use your test results?
Diagnosis
Your doctor looks for the Philadelphia chromosome and BCR-ABL1 gene to confirm your diagnosis of CML.
They also look for other chromosomal abnormalities. Your doctor will talk with you about any other changes and what they mean. For example, they will tell you if they find any changes that might affect how well you respond to treatment.
Response to treatment
The aim of treatment is to put your CML into remission. Remission means there are no signs of CML in your blood. The doctors refer to remission as ‘response to treatment’.
There are different tests that look for signs of CML. The test results provide information about how well the treatment is working to control your leukaemia.
Your doctor looks at:
- your full blood count and size of your spleen (haematological response)
- the amount of BRC-ABL1 gene in your blood (molecular response)
Your doctor may also look at the amount of Philadelphia chromosome in your blood and bone marrow (cytogenetic response), but this is rarely done these days.
