Tests for Acute Myeloid Leukemia (AML)

Certain signs and symptoms might suggest that a person could have acute myeloid leukemia (AML), but tests are needed to confirm the diagnosis.

Medical history and physical exam

The doctor will want to get a thorough medical history, focusing on your symptoms and how long you have had them. They might also ask about other health problems, as well as about possible risk factors for leukemia.

During the physical exam, the doctor will likely pay close attention to your eyes, mouth, skin, lymph nodes, liver, spleen, and nervous system, and will look for areas of bleeding or bruising, or possible signs of infection.

If there is reason to think there might be problems caused by low levels of blood cells (anemia, infections, bleeding or bruising, etc.), the doctor will most likely order blood tests to check your blood cell counts. You might also be referred to a hematologist, a doctor who specializes in diseases of the blood (including leukemia).

Types of samples used to test for AML

If the doctor thinks you might have leukemia, samples of cells from your blood and bone marrow will need to be checked to be sure. Other tissue and cell samples might also be taken to help guide treatment.

Blood samples

Blood tests are generally the first tests done to look for leukemia. Blood is taken from a vein in the arm.

Bone marrow samples

Leukemia starts in the bone marrow, so checking the bone marrow for leukemia cells is a key part of testing for it. Bone marrow samples are obtained from 2 tests that are usually done at the same time:

• Bone marrow aspiration
• Bone marrow biopsy

The samples are usually taken from the back of the pelvic (hip) bone, but sometimes other bones are used instead. If only an aspiration is to be done, it may be taken from the sternum (breastbone).

For a bone marrow aspiration, you lie on a table (either on your side or on your belly). The doctor will clean the skin over the hip and then numb the area and the surface of the bone by injecting a local anesthetic. This may cause a brief stinging or burning sensation. A thin, hollow needle is then inserted into the bone, and a syringe is used to suck out a small amount of liquid bone marrow. Even with the anesthetic, most patients still have some brief pain when the marrow is removed.

A bone marrow biopsy is usually done just after the aspiration. A small piece of bone and marrow is removed with a slightly larger needle that is pushed down into the bone. This may also cause some brief pain. Once the biopsy is done, pressure will be applied to the site to help prevent bleeding.

These bone marrow tests are used to help diagnose leukemia, but they might also be repeated later to tell if the leukemia is responding to treatment.

Spinal fluid

The cerebrospinal fluid (CSF) surrounds the brain and spinal cord. AML can sometimes spread to the area around the brain and spinal cord. To check for this spread, doctors might remove a sample of CSF for testing (a procedure called a lumbar puncture or spinal tap). A lumbar puncture is not often used to test for AML, unless a person is having symptoms that could be caused by leukemia cells that have spread into the brain and spinal cord.

For this test, you might lie on your side or sit up. The doctor first numbs an area of skin on the lower part of the back over the spine. A small, hollow needle is then inserted between the bones of the spine into the area around the spinal cord to remove some of the fluid.

A lumbar puncture is also sometimes used to deliver chemotherapy drugs into the CSF to help prevent or treat the spread of leukemia to the spinal cord and brain.

Lab tests used to diagnose and classify AML

One or more of the following lab tests may be done on the samples to diagnose AML and/or to determine the specific subtype of AML.

Complete blood count and peripheral blood smear

The complete blood count (CBC) is a test that measures the amounts of different cells in the blood, such as the red blood cells, white blood cells, and platelets. The CBC is often done along with a differential (or diff), which looks at the numbers of the different types of white blood cells. For the peripheral blood smear, a sample of blood is looked at under the microscope. Changes in the numbers and the appearance of different types of blood cells often help diagnose leukemia.

Most patients with AML have too many immature white cells in their blood, and not enough red blood cells or platelets. Many of the white blood cells may be myeloblasts (often just called blasts), which are very early forms of blood-forming cells that are not normally found in the blood. These cells don’t work like normal, mature white blood cells. These findings may suggest leukemia, but the disease usually is not diagnosed without looking at a sample of bone marrow cells.

Blood chemistry and coagulation tests

These tests measure the amounts of certain chemicals in the blood and the ability of the blood to clot. These tests are not used to diagnose leukemia, but they can help detect liver or kidney problems, abnormal levels of certain minerals in the blood, or problems with blood clotting.

Routine cell exams by microscope

Samples of blood, bone marrow, or CSF are looked at under a microscope by a pathologist (a doctor specializing in lab tests) and may be reviewed by the patient’s hematologist/oncologist (a doctor specializing in cancer and blood diseases).

The doctors will look at the size, shape, and other traits of the white blood cells in the samples to classify them into specific types.

A key element is whether the cells look mature (like normal blood cells) or immature (lacking features of normal blood cells). The most immature cells are called myeloblasts (or blasts).

The percentage of blasts in the bone marrow or blood is particularly important. Having at least 20% blasts in the marrow or blood is generally required for a diagnosis of AML. (In normal bone marrow, the blast count is 5% or less, while the blood usually doesn't contain any blasts.) AML can also be diagnosed if the blasts are found (using another test) to have a chromosome change that occurs only in a specific type of AML, even if the blast percentage doesn’t reach 20%.

Sometimes just counting and looking at the cells isn’t enough to provide a clear diagnosis. Other lab tests may be used to confirm an AML diagnosis.

Cytochemistry

For cytochemistry tests, cells are exposed to chemical stains (dyes) that react with only some types of leukemia cells. These stains cause color changes that can be seen under a microscope, which can help the doctor determine what types of cells are present. For instance, one stain can help distinguish AML cells from acute lymphocytic leukemia (ALL) cells. The stain causes the granules of most AML cells to appear as black spots under the microscope, but it does not cause ALL cells to change colors.

Flow cytometry and immunohistochemistry

For both flow cytometry and immunocytochemistry, samples of cells are treated with antibodies, which are proteins that stick only to certain other proteins on cells. For immunocytochemistry, the cells are then looked at under a microscope to see if the antibodies stuck to them (meaning they have these proteins), while for flow cytometry a special machine is used.

These tests are used for immunophenotyping – classifying leukemia cells according to the substances (antigens) on their surfaces. Leukemia cells can have different antigens depending on which type of cells they start in and how mature they are, and this information can be helpful in AML classification.

Chromosome tests

These tests look at the chromosomes (long strands of DNA) inside the cells. Normal human cells contain 23 pairs of chromosomes, each of which are a certain size and stain a certain way. AML cells sometimes have chromosome changes that can be seen under a microscope or found with other tests. Recognizing these changes can help identify certain types of AML and can be important in determining a patient’s outlook.

Cytogenetics: In this test, the cells are looked at under a microscope to see if the chromosomes have any abnormalities. A drawback of this test is that it usually takes about 2 to 3 weeks because the cells must grow in lab dishes for a couple of weeks before their chromosomes can be viewed.

The results of cytogenetic testing are written in a shorthand form that describes the chromosome changes:

• A translocation means parts of two chromosomes have traded places with each other. For example, if chromosomes 8 and 21 have swapped pieces, it would be written as t(8;21).
• An inversion, written as inv(16), for example, means that part of the chromosome 16 is now in reverse order but is still attached to the chromosome.
• A deletion, written as del(7) or -7, for example, indicates part of chromosome 7 has been lost.
• An addition or duplication, such as +8, for example, means that all or part of chromosome 8 has been duplicated, and too many copies of it are found within the cell.

Not all chromosome changes can be seen under a microscope. Other lab tests can often detect these changes.

Fluorescent in situ hybridization (FISH): This test looks more closely at cell DNA using special fluorescent dyes that only attach to specific genes or parts of particular chromosomes. FISH can find the chromosome changes (such as translocations) that are visible under a microscope in standard cytogenetic tests, as well as some changes too small to be seen with usual cytogenetic testing.

FISH can be used to look for changes in specific genes or parts of chromosomes. It can be used on regular blood or bone marrow samples without growing them in a lab first. This means the results are often available more quickly than with regular cytogenetic testing.

Polymerase chain reaction (PCR): This is a very sensitive test that can also find some gene and chromosome changes too small to be seen under a microscope. It is helpful in finding gene changes that are in only a few cells, making it good for finding small numbers of leukemia cells in a sample (like after treatment).

Other molecular and genetic tests

Other types of lab tests can also be done on the samples to look for specific gene or other changes in the leukemia cells. This is sometimes referred to as biomarker testing.

For example, the AML cells are often tested for changes (mutations) in genes such as FLT3, IDH1, and IDH2. People whose leukemia cells have changes in one of these genes are more likely to be helped by treatment with certain targeted therapy drugs.

Imaging tests for AML

Imaging tests use x-rays, sound waves, magnetic fields, or radioactive particles to create pictures of the inside of the body. Leukemia doesn’t usually form tumors, so imaging tests aren't often helpful in making the diagnosis. When imaging tests are done in people with AML, it's most often to look for infections or other problems, rather than to look for leukemia itself. In a few cases, imaging tests may be done to help determine the extent of the disease, if it's thought it might have spread beyond the bone marrow and blood.

X-rays

Routine chest x-rays may be done if a lung infection is suspected.

Computed tomography (CT) scan

A CT scan uses x-rays to make detailed, cross-sectional images of your body. This test can help show if any lymph nodes or organs in your body are enlarged. It isn’t usually needed to diagnose AML, but it may be done if your doctor suspects the leukemia is growing in an organ, like your spleen.

CT-guided needle biopsy: In some cases, a CT can be used to guide a biopsy needle into a suspected abnormality, such as an abscess. For this procedure, you lie on the CT scanning table while the doctor moves a biopsy needle through the skin and toward the mass. CT scans are repeated until the needle is within the mass. A sample is then removed and sent to the lab to be looked at under a microscope.

PET/CT: Some machines combine the CT scan with a PET scan (PET/CT scan). For a PET scan, glucose (a form of sugar) containing a radioactive atom is injected into the blood. Because cancer cells in the body grow rapidly, they absorb large amounts of the radioactive sugar. A special camera can then create a picture of areas of radioactivity in the body. With a PET/CT scan, the doctor can compare areas of higher radioactivity on the PET scan with the more detailed appearance of that area on the CT.

Magnetic resonance imaging (MRI)

Like CT scans, MRIs make detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays.

MRIs are very helpful in looking at the brain and spinal cord, but they are not usually needed in people with AML.

Ultrasound

Ultrasound uses sound waves and their echoes to make pictures of internal organs or masses.

Ultrasound can be used to look at lymph nodes near the surface of the body or to look inside your abdomen for enlarged lymph nodes or organs such as the liver, spleen, and kidneys. (It can’t be used to look inside the chest because the ribs block the sound waves.) It is sometimes used to help guide a biopsy needle into an enlarged lymph node.