Acute myeloid leukemia subtypes: FAB and WHO classifications

Acute myeloid leukemia (AML) is the The most common type of leukemia diagnosed in adults. The American Cancer Society estimates that 20,050 people will be diagnosed with AML in 2022.

AML goes by many other names, such as:

  • acute granulocytic leukemia
  • acute non-lymphocytic leukemia
  • acute myeloid leukemia
  • acute myeloid leukemia

Doctors divide AML into subtypes based on characteristics of the cancer cells. Identifying which subtype you have can be very important in determining the best treatment and predicting your outlook.

Read on to learn more about the subtypes of AML and the different systems used to classify them.

Doctors divide most types of cancer into stages based on the size of the tumor and how far it has spread. However, unlike most cancers, AML does not usually cause tumors. Doctors divide AML into subtypes rather than stages to predict outlook and guide treatment.

Two main classification systems have been used to categorize AML:

  1. Franco-American-British (FAB) system. A group of researchers created the FAB system in the 1970s. This system classifies AML into subtypes M0 through M7, primarily based on how the cancer cells look under the microscope.
  2. World Health Organization (WHO) system. The WHO system is now the main system used to classify AML. It takes into account more factors known to influence a person’s outlook, such as genetic mutations or “abnormalities” in chromosomes.

Diagnose AML subtypes

Diagnosing AML begins with a physical exam and a review of your medical history. If your doctor suspects blood cancer, they will order blood tests to help look for signs of leukemia. These often include:

  • a complete blood count to identify an abnormally high white blood cell count or low red blood cell and platelet count
  • a peripheral blood smear to look for atypical features in the size and shape of your blood cells

To confirm a diagnosis of LAM, doctors take a small sample of your bone marrow for laboratory analysis. This sample is usually taken from your hip bone.

The cells from your sample will be analyzed in the laboratory to distinguish your cancer from other types of leukemia and to look for certain genetic mutations. these trials include:

  • immunophenotyping (flow cytometry)
  • cytogenetic analysis (karyotyping)
  • polymerase chain reaction (PCR)
  • DNA sequencing

The FAB system classifies AML based on the type of cells in which the cancer grows and the maturity of those cells.

the subtypes in the FAB system are:

The WHO system is now the main system used to classify AML. the WHO International Classification of Diseases 11 (ICD-11)which became effective in January 2022, lists the following subtypes:

  • AML with recurrent genetic abnormalities. These subtypes are associated with certain genetic changes and are additionally categorized as:
    • LAM (megakaryoblastic) with a translocation between chromosomes 1 and 22
    • AML with chromosome 3 translocation or inversion
    • AML with a translocation between chromosomes 6 and 9
    • AML with a translocation between chromosomes 8 and 21
    • AML with a translocation between chromosomes 9 and 11
    • AML with chromosome 16 translocation or inversion
    • APL (acute promyelocytic leukemia) with the PML-RARA fusion gene
    • AML with the mutated MNP1 embarrassed
    • AML with two mutations of CEBPA embarrassed
    • LAM with the BCR-ABL1 (BCR-ABL) fusion gene (not yet known if this is a unique group)
    • LAM with mutated RUNX1 gene (not yet known if this is a unique group)
  • AML with changes related to myelodysplasia
  • treatment-related myeloid neoplasms
  • myeloid sarcoma
  • myeloid proliferations linked to Down syndrome
  • blast plasmacytoid dendritic cell neoplasm
  • LAM, not elsewhere classified. These AML subtypes do not fit into any of the other categories. They closely follow the FOB classification and include:
    • acute basophilic leukemia
    • acute panmyelosis with fibrosis
    • LAM with minimal differentiation (M0)
    • AML without maturation (M1)
    • AML with maturation (M2)
    • acute myelomonocytic leukemia (M4)
    • acute monoblastic/monocytic leukemia (M5)
    • pure erythroid leukemia (M6)
    • acute megakaryoblastic leukemia (M7)

A translocation occurs when one part of a chromosome changes to another.

Doctors use AML subtypes to help guide treatment decisions. The main treatment for most types of LAM is chemotherapy. Some types of AML like promyelocytic leukemia are treated with different drugs than other subtypes.

When determining the best treatment, doctors also consider other factors such as:

  • your age and general health
  • specific genetic mutations
  • chromosomal irregularities
  • markers on leukemia cells, such as the CD34 protein
  • blood cell count

Knowing your AML subtype can be very important in determining your prospects. Certain subtypes are linked to more favorable or less favorable outcomes.

For example, AML with changes related to myelodysplasia and treatment-related myeloid neoplasms tend to have a poor outlook compared to other types of AML.

Many other factors also play a role in determining your outlook and the intensity of your treatment. Doctors call these “prognostic factors.”

Chromosomal abnormalities

Atypical characteristics of AML cell chromosomes can also influence your outlook. Changes associated with a favorable outlook include:

  • translocation between chromosomes 8 and 21
  • translocation or inversion of chromosome 16
  • translocation between chromosomes 15 and 17

Atypical characteristics associated with an unfavorable outlook include:

  • loss of one of the two copies of a chromosome
  • loss of part of chromosome 5 or 7
  • abnormalities of chromosome 11
  • translocation between chromosomes 6 and 9
  • translocation or inversion of chromosome 3
  • translocation between chromosomes 9 and 22
  • changes involving three or more chromosomes

Other factors that affect the outlook

Other factors that affect your outlook include:

AML is a type of cancer that develops in immature blood cells. It is divided into subtypes based on how the cells look under the microscope and other factors, such as the presence of certain chromosomal abnormalities or genetic mutations.

Knowing which subtype you have can be important in determining the best treatment options and your outlook. Your doctor can explain which subtype you have and how it influences your treatment plan.

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