Morphology of acute myeloid leukemia (AML): what you need to know

Acute myeloid leukemia (AML) is cancer of the blood and bone marrow. It causes the bone marrow to produce abnormal myeloid cells.

Myeloid cells are responsible for the production of blood cells, such as platelets, red blood cells, and white blood cells called myeloblasts.

Health professionals classify AML into different subtypes based on their “morphology”. It refers to the characteristics of cancer cells, such as their size, structure and maturity.

Below, we outline the different morphologies of AML and explain how each can affect a person’s outlook. We are also exploring how doctors identify AML subtypes and whether their morphologies change over time.

Healthcare professionals can use one of these two systems to classify AML: the Franco-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 the more commonly used.

The FAB system distinguishes each type of AML based on two factors:

  • Leukemia cell line: This is the type of cell from which cancer has developed.
  • Cell differentiation stage: It refers to the maturity of cancer cells.

The FAB classification system begins with “M0” and ends with “M7” as follows:

  • Leukemia M0 to M5: These all come from immature white blood cells.
  • Leukemia M6: It comes from immature cells that would eventually become red blood cells. They are called precursor cells of red blood cells.
  • Leukemia M7: This comes from immature cells which would eventually develop into platelets.

The complete FAB classification system is:

  • M0: undifferentiated acute myelogenous leukemia
  • M1: acute myelogenous leukemia with minimal maturation
  • M2: acute myelogenous 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 can 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 types of AML with specific chromosomal changes.
  • AML with changes related to myelodysplasia: This includes the types of AML in people with a history of myelodysplastic syndrome and people with a higher percentage of abnormal-looking cells.
  • Treatment-related myeloid tumor: It involves cell damage resulting from previous chemotherapy or radiation therapy.
  • AML which is not otherwise specified: This includes AMLs that do not fit into any of the above categories.
  • Myeloid sarcoma: This is a solid tumor, also called a chromome or granulocytic sarcoma.
  • Myeloid proliferations associated with Down syndrome: This subtype of AML is associated with the genetic disease of Down syndrome.
  • Acute undifferentiated or biphenotypic leukemias: These are also called acute mixed phenotype leukemias. They are not strictly speaking AML but have characteristics of both lymphocytic and myeloid leukemia.

The outlook for people with AML may depend on the morphology of the disease – the specific characteristics of cancer cells, such as their size, structure, and maturity.

Healthcare professionals identify the morphology of AML by studying cancer cells under a microscope.

Chromosomal abnormalities

AML occurs as a result of a chromosomal translocation abnormality. It is a rupture of a chromosome which causes it to merge with a different chromosome. The fused chromosomes start to make abnormal proteins, which leads to the production of abnormal blood cells.

Anomalies related to a favorable outlook

These chromosomal abnormalities are associated with a better response to treatment and a more favorable overall outlook:

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

Anomalies associated with a less favorable outlook

These chromosomal abnormalities are associated with a less favorable response to treatment and the overall outlook:

  • 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
  • chromosome 11 abnormalities
  • loss of a chromosome, resulting in a cell having only one copy instead of two
  • changes involving three or more chromosomes

Genetic mutations

Genetic mutations within leukemia cells can also affect the outlook of a person 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, although newer drugs targeting this type of mutation may lead to better results.

He also says that people whose AML involves a mutation are in the CEBPA Where NPM1 genes tend to have a more favorable outlook.

However, a 2020 study suggests that people with both CEBPA and FLT3 genetic mutations tend to have a less favorable outlook.

The morphology of AML can change several times from diagnosis to relapse. According to a Study 2019, these changes can result from genetic or epigenetic causes. Epigenetic causes are behavioral or environmental factors that influence how genes work.

The same study notes that more than 60 genes can mutate recurrently in a person with AML.

To diagnose AML, a doctor usually orders blood and bone marrow samples.

A specialist called a pathologist examines cells under a microscope to determine if AML is present and, if so, the disease subtype. It is a question of evaluating:

  • the size of cancer cells
  • 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 cancer cells.
  • Chromosome tests: These involve examining the chromosomes inside the cells to identify any abnormalities.

AML is cancer of the blood and bone marrow, and there are many subtypes of it.

To determine the subtype, healthcare professionals examine cancer cells under a microscope to assess their size, shape, and maturity. They may also perform tests that involve staining cells, treating them with antibodies, or viewing their chromosomes.

The characteristics of AML cells can change repeatedly from diagnosis to relapse. Routine blood and bone marrow tests are important in monitoring the disease and determining the best treatment.

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