What Are the Acute Myelogenous Leukemia (AML) Subtypes?

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Determining the type of acute myelogenous leukemia (AML) someone has is much like staging other cancers, like lung or breast cancer. In solid tumor cancers like these, staging is important to determine the extent of the disease, and to help plan treatment. In the case of leukemia, however, doctors will instead look at tissue samples from bone marrow aspiration and biopsy to determine the acute myelogenous (or myeloblastic) leukemia subtype, and then determine next steps.

What Determines a Type of AML?

All blood cells, including red blood cells, platelets, and white blood cells, begin as a single stem cell in the bone marrow. Stem cells themselves do not have the ability to form clots, carry oxygen, or fight infection, but they develop or mature into fully functional blood cells that do.

Stem cells grow into immature blood cells, which look and act a little more like the "adult" cell they will eventually become with each stage of development they go through. Once the blood cell is mature enough to carry out its role in the body, it is released from the bone marrow and into the bloodstream, where it will remain for the rest of its life.

In the case of acute leukemia, there is an overproduction and release of very immature blood cells. The leukemia cells become "stuck" at one stage of development, and remain unable to do the function they are designed to do.

Types are determined by what stage of development the cells stop at.

There are two classification systems for identifying AML subtypes – the French-American-British (FAB) system and the World Health Organization (WHO) classification system.

The FAB is the one most commonly used. To classify AML using this system, doctors will look at the leukemia cells they obtain during the bone marrow biopsy. Beyond determining what stage of development the cells are at, they will also determine what kind of cell they were supposed to become when mature.

The chart below explains this system in greater detail.

Why Does My AML Subtype Matter?

Your AML subtype helps doctors to predict treatment, outcomes, prognosis, and behavior of your disease.

For example, researchers have learned that the M0, M4, and M5 subtypes are associated with lower remission rate and are less responsive to therapy. M4 and M5 subtype leukemia cells also are more likely to form masses called granulocytic sarcomas (lesions that form in soft tissue or bone) and to spread to the cerebrospinal fluid (CSF).

Treatment is the same for most subtypes of acute leukemia with the exception of APL (M3). Different medications are used to treat APL, and the prognosis tends to be better than with other types of acute leukemia.

The FAB Classification System

Subtype Subtype Name Frequency Cell Characteristics
M0 Myeloblastic 9- 12% Leukemia cells are extremely immature and do not have characteristics of the cell they were supposed to become.
M1 AML with minimal maturation 16- 26% Immature myeloid cells (or myeloblasts/ "blasts") are the main type of cell in the marrow sample.
M2 AML with maturation 20-29% Samples contain a lot of myeloblasts, but show more maturity than M1 subtype. Myeloblast is the last stage of development before the immature cell commits to becoming a white or red blood cell, or platelet
M3 Promyelocytic (APL) 1-6% Leukemia cells are still immature, between the myeloblast and myelocyte stage. Very under-developed, but starting to look and act more like a white cell.
M4 Acute Myelomonocytic Leukemia 16- 33% Leukemic cells are a mix of granulocytic and monocytic cell types The leukemia cells are looking more like white blood cells than the previous stage, but still very immature.
M5 Acute Monocytic Leukemia 9- 26% More than 80% of the cells are monocytes. May be at different stages of maturity.
M6 Acute Erythroid Leukemia 1-4% Leukemic cells are immature cells with characteristics of red blood cells.
M7 Acute Megakaryocytic Leukemia 0-2% Leukemic cells are immature with characteristics of platelets.

The Bottom Line

Because leukemia cells travel quickly throughout the body, traditional methods for staging cancer do not apply. Instead, doctors look at physical and genetic features of your bone marrow cells to assign it into a subtype. These subtypes help doctors to determine what type of treatment will work best for you and also help to predict the outcomes of your treatment.

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Article Sources

  • Aquino, V. “Acute Myelogenous Leukemia” Current Problems in Pediatrics February 2002 32:50-58.
  • Hillman, R. and Ault, K. (2002) The Acute Myeloid Leukemias. Hematology in Clinical Practice 3rd ed. New York McGraw- Hill.
  • Vardiman, J., Harris, N., and Brunning, R. “The World Health Organization (WHO) Classification of the Myeloid Neoplasms.” Blood October 2002 100: 2292- 2302.