Acute myeloid leukemia (AML), also known as acute myelogenous leukemia, is the most common type of acute leukemia in adults. It is responsible for about 20 percent of all childhood leukemias. About 30 percent of people living with AML experience disease that is resistant to treatment and eventually relapse. Classification of AML into the correct subtype is important to help determine the best treatment and monitoring plan for each situation.

Stages vs. Subtypes of AML

Acute myeloid leukemia begins in the bone marrow, and symptoms of AML usually don’t develop until it has spread to the blood. Because AML is usually detected once it has already spread to other organs, traditional cancer staging (based on whether cancer has spread) is not used.

Instead, AML is classified into subtypes based on blood cell counts, how the leukemia cells look under the microscope, identification of genetic abnormalities, and the type of white blood cell that has become cancerous.

Each type of AML has different unique features, probable symptoms, and optimal treatments. Typically, the more advanced the disease is, the more difficult it is to treat. Your doctor may also use a prognostic test to help determine your outlook and figure out what treatments are best for your specific situation.

Classifying Acute Myeloid Leukemia Subtypes

There are two classification systems for AML: the older French-American-British (FAB) classification system and the newer World Health Organization (WHO) classification system. Doctors may use imaging tests, genetic tests, blood tests (such as complete blood counts), and bone marrow biopsies to help classify AML.

French-American-British System

The FAB classification system groups AML into subtypes M0 to M7 based on how the abnormal cells look under a microscope, with additional information from special cell stains:

• M0 undifferentiated acute myeloblastic leukemia — The cells in the bone marrow are immature white blood cells (called blast cells or myeloblasts) but do not possess specific changes found in other groups.
• M1 myeloblastic leukemia — Myeloblasts have small signs of cancerous changes, including overgrowth of some immature white blood cells.
• M2 myeloblastic leukemia — Myeloblasts have begun to mature incorrectly into an abnormal type of white blood cell.
• M3 promyelocytic leukemia — Myeloblasts have further matured incorrectly. The cancerous cells may contain small particles, and their nuclei (where DNA is stored) may start to change in size and shape.
• M4 myelomonocytic leukemia — In this subtype, abnormal cells that originate in the bone marrow have started to move into the blood, and the bone marrow contains more than 20 percent abnormal cells. This subtype may also occur along with a white blood cell disorder known as eosinophilia.
• M5 monocytic leukemia — There are increased numbers of abnormal cells in the blood and bone marrow, and the genetic material in cancer cells may look abnormal under a microscope.
• M6 erythroleukemia — This subtype arises when immature red blood cells have begun to develop abnormally.
• M7 megakaryoblastic leukemia — Immature forms of platelets, another type of white blood cell, are present in the bone marrow along with many fibrous tissue deposits (fibrosis).

WHO System

The newer WHO classification system uses many factors and the probable cause of AML to group the disease into different subtypes. There are several categories under the WHO system, and correct classification can help determine the best plan for treatment and monitoring.

AML With Gene Changes or Chromosome Rearrangements

AML frequently has genetic changes, including translocations that involve rearrangements of whole chromosomes. There are several subtypes of AML in this category, including:

• AML with a translocation between chromosomes 8 and 21 [t(8;21)]
• AML with a translocation or inversion in chromosome 16 [t(16;16) or inv(16)]
• APL with the PML-RARA fusion gene
• AML with a translocation between chromosomes 9 and 11 [t(9;11)]
• AML with a translocation between chromosomes 6 and 9 [t(6:9)]
• AML with a translocation or inversion in chromosome 3 [t(3;3) or inv(3)]
• AML (megakaryoblastic) with a translocation between chromosomes 1 and 22 [t(1:22)]
• AML with the BCR-ABL1 (BCR-ABL) fusion gene
• AML with a mutated NPM1 gene
• AML with biallelic mutations of the CEBPA gene (mutations in both copies of the gene)
• AML with a mutated RUNX1 gene (this is still a provisional entity — it’s not yet clear if there’s enough evidence that it’s a unique group)

AML With Myelodysplasia-Related Changes

This type of AML is related to precancerous changes in the bone marrow (myelodysplasia).

Therapy-Related AML

AML is a potential late side effect associated with previous cancer treatment, especially chemotherapy or radiation therapy.

AML Not Otherwise Specified

AML not otherwise specified includes cases with unknown causes that do not fit into the other groups. Subtypes are similar to the FAB classification and include:

• AML with minimal differentiation (FAB M0)
• AML without maturation (FAB M1)
• AML with maturation (FAB M2)
• Acute myelomonocytic leukemia (FAB M4)
• Acute monoblastic/monocytic leukemia (FAB M5)
• Pure erythroid leukemia (FAB M6)
• Acute megakaryoblastic leukemia (FAB M7)
• Acute basophilic leukemia
• Acute panmyelosis with fibrosis

Myeloid Sarcoma

Myeloid sarcoma (also called granulocytic sarcoma or chloroma) is a more advanced form of disease that includes a tumor made of immature myeloid cells.

AML Related to Down Syndrome

Cancer can arise from the overgrowth of myeloid cells related to another genetic disease, Down syndrome.

Mixed-Phenotype Acute Leukemias

Mixed-phenotype acute leukemias have features of both lymphocytic cells (pertaining to lymphoid tissue like the spleen) and myeloid cells (pertaining to bone marrow cells). They include immature (undifferentiated) leukemias and acute leukemias with different presentations (called biphenotypic acute leukemias).

Subtype and Prognosis Scores for Acute Myeloid Leukemia

Doctors take into account various prognostic factors when deciding how to treat AML, including the following:

• A person’s age
• White blood cell (lymphocyte) or platelet count
• A personal or familial history of blood disorders
• Whether the leukemia was preceded by a myelodysplastic syndrome
• Prognostically significant genetic changes, such as specific gene mutations or chromosomal abnormalities
• Overall medical condition

Adult AML can be categorized into favorable, intermediate, and adverse-risk groups based on its cellular characteristics. Within these categories, there is a lot of variation between individual cases of AML and their prognosis (disease outlook).

To determine a prognosis score for AML, doctors take into account the subtype of AML, the types and maturity of cells in the blood and bone marrow, and chromosomal abnormalities. Using these risk factors and one of several scoring systems, doctors can assign a number to each prognostic factor based on its severity. For example, having impaired organ function or certain genetic changes may suggest a specific prognosis or treatment strategy. Scores for each factor are added to come up with the risk score. The overall risk score describes the rate of disease progression.

This prognostic score helps health care professionals choose the best treatment option for each individual living with AML. Cancers with a higher grade, stage, or prognostic score are typically more aggressive (faster-growing) and are treated with a more intensive regimen.

Talk With Others Who Understand

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