Doctors perform a number of tests on blood and bone samples to make the diagnosis of CML in people suspected of having the disease. The following is a summary of the tests and what they tell you.
Bone marrow aspiration and biopsy: For this test, the person lies on a table and is injected in the hip area with the anesthetic to numb the skin and bone. A thin needle is inserted into the bone and a teaspoonful of bone marrow (the soft part inside the bone) is removed for analysis. For the biopsy, a small piece of bone (about a centimeter in length) and marrow is removed.
The blood and bone samples are examined under a microscope. What is important is the size, shape and type of cells. Normal bone marrow contains blood-forming cells and fat cells. In people with CML, the marrow is often hypercellular, i.e. there are too many blood-forming cells because of leukemia.
Blood count: A sample of blood is removed from a vein (usually in the arm). A complete blood count (CBC) measures the number of different blood cells, such as red blood cells (RBC), white blood cells (WBC), and platelets. The CBC often includes a differential, which counts the relative number of different types of WBCs (the main types are neutrophils, eosinophils, basophils, lymphocytes and monocytes). In people with CML, there are too many WBCs and a higher proportion are immature (not fully developed) because of the rapid proliferation of white blood cells that is the characteristic feature of CML. The most immature of these blood-forming cells are called “blasts” or “myeloblasts”. The high number of WBCs can also crowd out other types of blood cells, so the person may have low numbers of RBCs (which may result in anemia) and platelets (called thrombocytopenia, which can result in bruising or bleeding).
Genetic testing: CML is generally caused by a mutation that is acquired (i.e. you didn’t inherit it from your parents, and you don’t pass it along to your children). Three types of genetic tests may be performed during the diagnosis of CML.
- Cytogenetics: This looks at chromosomes under a microscope to see if there are any changes. Of particular importance is the Philadelphia chromosome, which appears as a shortened version of chromosome 22 (people have 23 pairs of chromosomes) and which is found in most people with CML. This truncated chromosome is caused by breaks in chromosomes 9 and 22, which then swap pieces with each other. The location of the break is called the breakpoint cluster region, or BCL, which fuses with the ABL gene to create the “CML gene” (called BCR-ABL).
- FISH (or fluorescent in situ hybridization): This test tags specific parts of the chromosomes with special fluorescent dyes as a way of detecting the presence of BCR-ABL.
- Polymerase chain reaction (PCR): This technique subjects a sample of blood or bone to a series of chemical tests, which serve to amplify a genetic sequence into millions of copies. This means the PCR is a highly sensitive method for detecting the BCR-ABL gene in cells. So PCR can identify the presence of CML when less sensitive tests (such as cytogenetics or FISH) have failed to detect it. Once CML has been diagnosed, PCR is used to determine how well treatment (a TKI such as Gleevec, Tasigna or Sprycel) is suppressing the function of the BCR-ABL leukemia gene. This is done by measuring the amount of signalling proteins (called BCR-ABL transcripts) being produced by the gene. A lowering number of transcripts means that BCR-ABL is less active and/or fewer copies of the gene are present.
Imaging: CML typically causes the spleen to become enlarged. This can be visualized with imaging techniques, such as a CT (computed tomography) scan or ultrasound.
For a CT, you lie on a table and X-rays are taken from various angles; a computer then combines these images into a detailed picture of your spleen and other internal organs.
With an ultrasound, the technician will apply a lubricant to your skin and will then pass a small handheld device (called a transducer) over the surface of your body. Ultrasound functions essentially the same way as sonar or a bat’s echolocation. The transducer emits sound waves and listens to the echoes as the sound bounces off your internal organ. A computer then converts this information into an image on a computer screen. This is useful for imaging the spleen and lymph nodes to see if they are enlarged.