Many people with CML do not have symptoms when diagnosed. The most common sign of CML is an abnormal white blood cell count often found during blood tests for an unrelated health problem or during a routine checkup. To diagnose CML, doctors use a variety of tests to analyze blood and bone marrow cells. A pathologist, a doctor who specializes in identifying diseases by studying cells under a microscope, will examine the blood cells and the bone marrow cells. The samples should also be examined by a hematopathologist, a specialist who diagnoses diseases of the blood and marrow.
Tests that are used to diagnose CML
Complete Blood Count (CBC) with Differential. This test is used to measure the number red blood cells, white blood cells and platelets in a sample of blood. It also measures the amount of hemoglobin in the red blood cells and the percentage of red blood cells in the sample. The CBC should include a differential. The differential measures the different types of white blood cells in the sample.
People with CML often have
- An increased white blood cell count, often to very high levels
- A decreased red blood cell count
- A possible increase or decrease in the number of platelets, depending on the severity of the person’s CML.
Peripheral Blood Smear. Blood cells are stained (dyed) and examined with a light microscope. These samples show
- The number, size, shape and type of blood cells
- Specific pattern of white blood cells
- The proportion of immature cells (blast cells) compared to the proportion of maturing and fully matured white blood cells. Blast cells are normally not present in the blood of healthy individuals.
Bone Marrow Aspiration and Biopsy. These tests are used to examine bone marrow cells to find abnormalities, and are generally done at the same time. The sample is usually taken from the patient’s hip bone after medicine has been given to numb the skin. For a bone marrow aspiration, a hollow needle is inserted through the hip bone and into the bone marrow to remove a liquid sample of cells. For a bone marrow biopsy, a wider needle is used to remove a small piece of bone that contains marrow. Both samples are examined under a microscope to look for chromosomal and other cell changes.
Cytogenetic Analysis. Cytogenetics is the study of chromosomes and chromosomal abnormalities. Samples from the bone marrow are examined under a microscope for chromosomal changes or abnormalities such as the Philadelphia (Ph) chromosome. The presence of the Ph chromosome in the bone marrow cells, along with a high white blood cell count and other characteristic blood and bone marrow test findings, confirm the diagnosis of CML. The bone marrow cells of about 95 percent of people with CML have a Ph chromosome that is detectable by cytogenetic analysis. A small percentage of people with clinical signs of CML do not have cytogenetically detectable Ph chromosome, but they almost always test positive for the BCR-ABL1 fusion gene on chromosome 22 with other types of tests.
FISH (Fluorescence In Situ Hybridization). FISH is a laboratory test used to examine genes and chromosomes in cells. FISH is a more sensitive method for detecting CML than the standard cytogenetic tests that identify the Ph chromosome. FISH can identify the presence of the BCR-ABL1 gene. Genes are made up of DNA segments. FISH uses color probes that bind to DNA to locate the BCR and ABL1 genes in chromosomes. Both BCR and ABL1 genes are labeled with different chemicals, each of which releases a different color. The color shows up on the chromosome that contains the gene—normally chromosome 9 for ABL1 and chromosome 22 for BCR—so FISH can detect the piece of chromosome 9 that has moved to chromosome 22 in CML cells. The BCR-ABL1 fusion gene is shown by the overlapping colors of the two probes.
Quantitative Polymerase Chain Reaction (qPCR). qPCR is the most sensitive test that detects and measures the quantity of the BCR-ABL1 gene in blood or bone marrow samples. It can detect very small amounts of the BCR-ABL1 gene (even when the Ph chromosome cannot be detected in blood or bone marrow cells with cytogenetic testing) to a level of one CML cell in a background of 100,000 to 1,000,000 normal cells.
Blood cell counts, bone marrow examinations, FISH and qPCR may also be used to track a person’s response to therapy once treatment has begun. qPCR testing is recommended every 3 months for 2 years as long as the patient’s CML is responding to treatment. After 2 years, the test should be done every 3 to 6 months.
For detailed information, access the free information booklet, Chronic Myeloid Leukemia.
See what doctors and patients say about the value of PCR testing: