Acute myeloid leukemia (AML) is a type of cancer that begins in the blood-forming cells of the bone marrow. Doctors do not stage AML like many other cancers, as it does not typically form tumors. Instead, experts can classify AML into subtypes, which can help them provide the most suitable treatments.

AML is the most common type of acute leukemia among adults. Some research estimates that 20,240 people will receive a diagnosis of AML in 2021.

Some people may refer to AML as acute myelogenous leukemia, acute myeloblastic leukemia, acute granulocytic leukemia, or acute nonlymphocytic leukemia.

Doctors can use classification systems to classify AML subtypes based on the specific characteristics of the blood cells. By identifying the subtype and prognostic factors, such as age, doctors can provide the best treatment options and improve a person’s outlook.

This article discusses AML, including its subtypes according to the two most commonly used classification systems for AML. It also looks at the identification, outlook, and relapse risk of AML.

A nurse drawing a blood sample so doctors can identify the type of AML the person has.Share on Pinterest
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The French-American-British (FAB) classification for acute leukemias is an older classification system that people have used since the 1970s. However, doctors still commonly use it today.

This classification system relies on how the cells appear under a microscope. Knowing this helps doctors identify their cell lineage and degree of maturation.

The FAB classification divides AML into subtypes M0 to M7 as follows:

  • M0: undifferentiated acute myeloblastic leukemia
  • M1: acute myeloblastic leukemia with little or no maturation
  • M2: acute myeloblastic leukemia with maturation
  • M3: acute promyelocytic leukemia (APL)
  • M4: acute myelomonocytic leukemia
  • M4eo: acute myelomonocytic leukemia with eosinophilia
  • M5: acute monocytic leukemia
  • M6: acute erythroid leukemia
  • M7: acute megakaryoblastic leukemia

The World Health Organization (WHO) classification for AML is the more recent and extensively used system for classifying AML.

Unlike the FAB classification, the WHO classification considers factors that affect a person’s outlook. Characteristics such as genetic irregularities, biologic features, and the effects of previous exposure to therapy all affect the clinical presentation and outlook of the AML.

The WHO Classification of Tumours, Revised 4th Edition, Volume 2 — published in 2017 — divides AML into the following general groups:

  • AML with recurrent genetic abnormalities
  • AML with myelodysplasia-related changes
  • therapy-related myeloid neoplasms
  • AML not otherwise specified
  • myeloid sarcoma
  • myeloid proliferations associated with Down syndrome

Doctors can identify the specific AML type by analyzing leukemic cells from the person’s bone marrow and blood samples.

Specifically, specialists use tests to look at their shape, size, and appearance (morphology), cell components and composition (cytochemistry), and the presence of markers, or antigens, on the cell’s surface to determine their function (immunophenotyping).

These tests include:

  • Peripheral blood smear: An expert will look at a sample of blood under a microscope to identify changes in the number and appearance of different types of blood cells.
  • Cytochemistry: This test uses dyes to cause certain leukemic cells to change colors. This can help specialists determine what types of cells are present in the sample.
  • Immunophenotyping: This test is essential in classifying AML by looking at markers, or antigens, on the cell’s surface to help determine which type of cell they start in and how mature they are.
  • Cytogenetics: This chromosome test looks at cells under a microscope to see if a person’s chromosomes have any irregularities. Chromosomal changes that this test can detect include translocations, inversions, deletions, additions, and duplications.
  • Fluorescent in situ hybridization: This is another chromosome test that uses special fluorescent dyes that attach only to certain parts of chromosomes or specific genes.
  • Polymerase chain reaction: This is a sensitive test that can identify changes too small for an expert to see under a microscope. It is useful for detecting the presence of low numbers of leukemic cells in a sample.

People with AML respond variably to treatment because of diverse genetic and clinical presentations. Some factors that affect AML outlook include a person’s AML subtype, age, and treatment response. The sections below look at each of these factors in more detail.

Age

People older than 60 years of age typically have a poorer outlook than younger individuals. This may be because older adults have more chromosomal irregularities and other medical conditions.

Response to initial treatment

People who respond well to treatment and attain complete remission upon initial treatment typically have better survival outcomes than those who do not respond to treatment or who relapse within the first 6 months.

Chromosomal irregularities

Around 50–60% of people with AML have cytogenetic irregularities. Certain cytogenetic, or chromosomal, irregularities are associated with better outcomes, while others may suggest poorer outcomes.

For example, APL is a subtype of AML. The FAB classification categorizes it as an M3 subtype, and the WHO classification categorizes it as APL with a translocation between chromosomes 15 and 17.

Due to advances in diagnostic techniques and treatments, many experts consider APL to be one of the more curable subtypes of AML in adults. It has complete remission and cure rates of roughly 90% and 80%, respectively.

Gene mutations

Some research notes that genetic mutations can affect how people respond to certain treatments, with some mutations associated with better outcomes.

For example, having mutations in the NPM1 gene is associated with a higher likelihood of complete remission, improved overall survival, and a lower incidence of relapse.

Meanwhile, evidence from European LeukemiaNet indicates that mutations in the TP53 gene are associated with particularly poor survival rates.

Markers in leukemic cells

Doctors also use antigens in leukemic cells to determine prognosis. People who highly express CD56 typically have worse outlooks and poorer overall survival rates.

Some research also suggests that people with blasts on peripheral blood with high expression of CD87 also have poorer outlooks and are likely to relapse.

Other conditions

People with a history of myelodysplastic syndrome or another blood disorder and people who develop AML from treatments for other cancer types, known as therapy-related AML, also have poorer outlooks.

With appropriate and intensive treatment, around 60–70% of people with AML will experience complete remission after initial treatment.

However, around half of these people will relapse months to years after treatment, with most relapses happening 2–3 years later. Although rare, about 1–3% of people experience a late relapse, occurring at least 5 years after remission.

One 2020 paper mentions that the burden of relapse is high in people who have received allogeneic stem cell transplants and induction chemotherapy.

Learn more about AML and chemotherapy here.

AML is a type of leukemia with many subtypes that have diverse clinical presentations and respond differently to treatment due to several different factors.

Classification systems can identify AML subtypes based on these clinical features and characteristics, which are helpful in determining the diagnosis, treatment, and outlook for people with AML.

Aside from AML subtype, other factors affecting outlook — such as age and the presence of gene mutations — can impact the outcome of AML. Although treatment advances are leading to better outlooks, people with AML — including those who have achieved complete remission after their initial treatment — may still be at risk of relapse.