Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow. It causes the bone marrow to produce abnormal myeloid cells.
Myeloid cells are responsible for producing blood cells, such as platelets, red blood cells, and white blood cells called myeloblasts.
Medical professionals categorize AML into different subtypes according to their “morphology.” This refers to features of the cancerous cells, such as their size, structure, and maturity.
Below, we describe the different AML morphologies and explain how each may affect a person’s outlook. We also explore how doctors identify AML subtypes and whether their morphologies change over time.
Medical professionals may use one of these two systems for classifying AML: the French-American-British (FAB) system or the World Health Organization (WHO) system.
FAB classification system
This is the more traditional of the two systems, and it is more commonly used.
The FAB system distinguishes each AML type based on two factors:
- Leukemia cell lineage: This refers to the type of cell that the cancer has developed from.
- Stage of cell differentiation: This refers to how mature the cancer cells are.
The FAB classification system begins with “M0” and runs through to “M7” as follows:
- M0 to M5 leukemias: These all derive from immature white blood cells.
- M6 leukemia: This derives from immature cells that would eventually become red blood cells. They are called red blood cell precursor cells.
- M7 leukemia: This derives from immature cells that would eventually develop into platelets.
The full FAB classification system is:
- M0: undifferentiated acute myeloblastic leukemia
- M1: acute myeloblastic leukemia with minimal maturation
- M2: acute myeloblastic leukemia with maturation
- M3: acute promyelocytic leukemia
- M4: acute myelomonocytic leukemia
- M4 eos: acute myelomonocytic leukemia with eosinophilia
- M5: acute monocytic leukemia
- M6: acute erythroid leukemia
- M7: acute megakaryoblastic leukemia
WHO classification system
This system takes into account additional factors that may affect a person’s outlook, such as genetic abnormalities and molecular markers.
The WHO classification system is as follows:
- AML with recurrent genetic abnormalities: This includes AML types with specific chromosome changes.
- AML with myelodysplasia-related changes: This includes AML types in people with a history of myelodysplastic syndrome and people with a higher percentage of cells that have an abnormal appearance.
- Therapy-related myeloid neoplasm: This involves cell damage resulting from previous chemotherapy or radiation therapy.
- AML that is not otherwise specified: This includes AMLs that do not fall into any of the above categories.
- Myeloid sarcoma: This involves a solid tumor, which is also referred to as a chroloma or a granulocytic sarcoma.
- Myeloid proliferations related to Down syndrome: This AML subtype is associated with the genetic condition Down syndrome.
- Undifferentiated or biphenotypic acute leukemias: These are also called mixed phenotype acute leukemias. These are not strictly AMLs but have features of both lymphocytic and myeloid leukemias.
The outlook for people with AML can depend on the disease’s morphology — the specific features of the cancerous cells, such as their size, structure, and maturity.
Medical professionals identify AML morphology by studying the cancerous cells under a microscope.
AML occurs as a result of a chromosomal abnormality of translocation. This is a break in a chromosome that causes it to fuse to a different chromosome. The fused chromosomes begin making abnormal proteins, which lead to the production of abnormal blood cells.
Abnormalities linked to a favorable outlook
These chromosomal abnormalities are associated with a better response to treatment and a more favorable outlook overall:
- a translocation between chromosomes 8 and 21
- a translocation or inversion of chromosome 16
- a translocation between chromosomes 15 and 17
Abnormalities associated with a less favorable outlook
These chromosomal abnormalities are associated with a less favorable response to treatment and overall outlook:
- the loss of part of chromosomes 5 or 7
- a translocation or inversion of chromosome 3
- a translocation between chromosomes 6 and 9
- a translocation between chromosomes 9 and 22
- abnormalities of chromosome 11
- the loss of a chromosome, resulting in a cell having only one copy instead of two
- changes involving three or more chromosomes
Genetic mutations within leukemia cells can also affect the outlook for someone with AML.
The American Cancer Society reports that people whose AML involves a mutation in the FLT3 gene tend to have a less favorable outlook, though new drugs targeting this type of mutation may lead to better outcomes.
It also says that people whose AML involves a mutation in either the CEBPA or NPM1 genes tend to have a more favorable outlook.
However, a 2020 study suggests that people with both CEBPA and FLT3 gene mutations tend to have a less favorable outlook.
The morphology of AML can change repeatedly from diagnosis to relapse. According to a
The same study notes that more than 60 genes may recurrently mutate in a person with AML.
To diagnose AML, a doctor typically requests samples of blood and bone marrow.
A specialist called a pathologist looks at the cells under a microscope to determine whether AML is present, and if so, the disease’s subtype. This involves assessing:
- the cancerous cells’ size
- their shape
- their maturity
- the percentage of these cells in the sample
The doctor may need to order additional lab tests to identify or confirm the AML subtype. These may include:
- Cytochemistry: This involves staining the cells with dyes to identify the types present in the sample.
- Flow cytometry and immunohistochemistry: This involves treating the samples with antibodies that stick to certain proteins on certain cancerous cells.
- Chromosome tests: These involve looking at the chromosomes inside the cells to identify any abnormalities.
AML is a cancer of the blood and bone marrow, and it has many subtypes.
To determine the subtype, medical professionals look at the cancerous cells under a microscope to assess their size, shape, and maturity. They may also perform tests that involve staining the cells, treating them with antibodies, or viewing their chromosomes.
The characteristics of AML cells may change repeatedly from diagnosis to relapse. Routine blood and bone marrow tests are important for monitoring the disease and determining the best treatment.