Acute Myeloid Leukemia Diagnosis and Staging

April 19, 2024 
This page was reviewed under our medical and editorial policy by Guido Marcucci, M.D., Chair, Department of Hematologic Malignancies Translational Science, City of Hope Duarte

The most common type of acute leukemia in adults, acute myeloid leukemia (AML) is a cancer that affects the blood and bone marrow. AML is diagnosed through a variety of blood tests, a thorough medical history and a physical exam. The goal is to learn as much as possible about the cancer by identifying its subtype and other important characteristics, all of which will help guide treatment decisions.

AML Diagnosis and Detection

Diagnosing AML typically starts with a thorough medical history, focusing on any symptoms and risk factors for leukemia. A physical exam follows, with close attention paid to the eyes, mouth, skin, lymph nodes, liver, spleen and nervous system. Signs of AML that may be evident during a physical exam include bleeding, bruising or signs of infection.

Blood tests are generally the first tests to look for leukemia, including AML. The testing starts with a complete blood count (CBC), which counts the different cells, including red blood cells, white blood cells and platelets. A CBC is often done with a differential blood test that tallies the different types of white blood cells specifically.

A peripheral blood smear may follow. This test involves examining a blood sample under a microscope.

AML occurs when the production of abnormal white blood cells surges dramatically. This surge prevents the production of healthy red blood cells, platelets and mature white cells, or leukocytes. Most people with AML have too many immature white cells in their blood and not enough red blood cells or platelets.

Bone Marrow Aspiration and Biopsy

Leukemia starts in the bone marrow — the soft, spongy tissue inside the bones — so an examination of bone marrow cells will be needed.

During a bone marrow aspiration, a hollow needle is used to extract a sample of bone marrow, blood and bone tissue from the hip bone or breastbone. A local anesthetic is used to numb the area so a patient may have only a brief stinging or burning feeling. A pathologist then examines the sample for evidence of leukemia.

A bone marrow biopsy is usually done just after the aspiration. In this procedure, a small piece of bone marrow is removed, using a slightly larger needle.

AML is diagnosed when the bone marrow is made up of at least 20% myeloblasts (also called blasts), which are immature white cells. Normal marrow has 5% or fewer blasts.

The doctor may also order a lumbar puncture or spinal tap to see if AML has spread to the brain and spinal cord. This test is not used to diagnose AML unless symptoms suggest the need for it.

Cytochemistry

During cytochemistry testing, a sample of blood or bone marrow cells is exposed to dyes that react with specific leukemia cells. This staining process may help distinguish AML cells from those seen in other types of leukemia. 

Flow cytometry and immunohistochemistry testing may help classify leukemia cells according to the antigens on their surfaces. Antigens are substances that prompt the body to create protective antibodies.

Chromosome tests examine strands of genetic material inside the cells. This may be done by examining cells under a microscope or using other types of testing. Fluorescent in situ hybridization (FISH), for example, looks more closely at DNA using special fluorescent dyes that attach only to specific genes or parts of particular chromosomes. FISH may be used on regular blood or bone marrow samples without growing them in a lab, so results are often available more quickly.

Polymerase chain reaction (PCR) testing may be used to find genetic and chromosome changes that are too small to be seen under a microscope.

With PCR tests, doctors analyze how a tissue sample reacts to certain chemicals to narrow down a leukemia diagnosis.

Additional Molecular and Genetic Tests

Other molecular and genetic tests for AML may include the following.

Biomarker testing: This is used to identify specific genetic or other changes within leukemia cells. The specific biomarkers identified can help guide acute myeloid leukemia treatment decisions.

Genetic testing: AML cells may also be tested for mutations, or changes, in genes such as FLT3, IDH1 and IDH2.

The more information a medical team has, the more help it provides in guiding treatment decisions.

AML Screening

There is no AML screening test for people who are at average risk of cancer. One way to spot this disease early is to keep an eye out for AML symptoms and seek medical guidance if they develop.

Certain individuals may be at higher risk for developing AML, including:

• People with certain blood disorders, such as myelodysplastic syndromes
• People with inherited disorders, such as Down syndrome
• People treated with chemotherapy or radiation therapy for another type of cancer
• People with a personal or family history of leukemia
• Current or past smokers
• People exposed to radiation in the environment

Acute Myeloid Leukemia Stages

AML isn’t staged in the same way that solid tumors are. Instead, AML is classified by subtypes, based on the maturity of the cells or genetic abnormalities.

AML Subtypes

Two systems may be used to classify AML into its subtype.

The World Health Organization (WHO) system is the most recent approach to staging, accounting for genetic and other factors that have been found to affect a patient’s prognosis. Its classifications divide AML into the following groups.

1. AML with certain gene or chromosome changes, such as:
   • AML with a translocation between chromosomes 8 and 21. (A translocation occurs when one chromosome breaks off and reattaches to another.)
   • AML with a translocation or inversion in chromosome 16.
   • APL with the PML-RARA fusion gene.
   • AML with a translocation between chromosomes 9 and 11.
   • AML with a translocation between chromosomes 6 and 9.
   • AML with a translocation or inversion in chromosome 3.
   • Acute megakaryoblastic leukemia with a translocation between chromosomes 1 and 22.
   • AML with the BCR-ABL1 (BCR-ABL) fusion gene. (It’s not known if this is a unique group.)
   • AML with mutated NPM1 gene.
   • AML with mutations in both copies of the CEBPA gene.
   • AML with mutated RUNX1 gene. (It’s not yet known if this is a unique group.)
2. AML with myelodysplasia-related changes, such as those with at least 20% of blood or bone marrow comprising immature white blood cells (myeloblasts) and other characteristics.
3. AML related to previous chemotherapy or radiation.
4. Myeloid sarcoma granulocytic sarcoma or chloroma.
5. Myeloid proliferations related to Down syndrome.
6. Undifferentiated and biphenotypic acute leukemias or mixed phenotype acute leukemias with lymphocytic and myeloid features.

The French-American-British (FAB) classification system for AML divides AML into subtypes M0 through M7. This classification is based on the type of cell from which the leukemia develops and the maturity of the cells. This information may be gleaned by looking at leukemia cells under the microscope after staining.

In general, AML subtypes M0 through M5 start in immature white blood cells, while M6 AML starts in very immature red blood cells. M7 AML begins in immature forms of platelet-making blood cells.

Other classifications may be helpful as well. In AML, the type of abnormal chromosomal change and its location signals different prognoses and treatment plans. Chromosomes — structures that carry DNA and proteins — may break off and move to a new location, repeat in number or be missing. In terms of prognosis, different chromosomal changes may be classified as favorable, intermediate or unfavorable.

The specific genes that are involved for each patient and whether or not the AML is recurrent also help to classify the disease.