Classification of acute myelogenous leukemia

Acute myelogenous leukemia (AML) starts in abnormal myeloid stem cells. Myeloid stem cells normally develop into red blood cells (also called erythrocytes), white blood cells (either granulocytes or monocytes) or platelets (also called megakaryocytes).

AML is usually classified by the World Health Organization (WHO) system or the French-American-British (FAB) system. Rarely, acute leukemia may have characteristics of both AML and acute lymphocytic leukemia (ALL). These rare leukemias are referred to as mixed phenotype acute leukemias (MPAL).

WHO classification system

The WHO system is newer than FAB. It uses cell characteristics and genetics to classify AML into several broad categories.

There are many chromosome abnormalities seen in AML. Common abnormities include:

• translocation (part of a chromosome is transferred to another chromosome) of chromosomes 8 and 21, 15 and 17 or 9 and 11
• inversion of chromosome 16
• deletion of part or all of chromosome 5 or 7
• an extra chromosome 8 (called trisomy 8)

Some people with AML have changes, or mutations, in certain genes, including:

• FMS-like tyrosine kinase 3 (FLT3) gene
• nucleophosmin (NPM1) gene
• overexpression of the ERG gene

The WHO system uses these chromosome abnormalities and gene mutations, along with other factors, to classify AML as the following subtypes.

AML with certain genetic abnormalities

WHO uses specific genetic abnormalities to classify the following types of AML:

• AML with a translocation between chromosomes 8 and 21
• AML with abnormal eosinophils and a translocation or inversion in chromosome 16
• AML with changes in chromosome 11
• APL (M3), which usually has a translocation between chromosomes 15 and 17

AML with myelodysplasia-related changes

With this type of AML, more than one type of myeloid cell is abnormal, or dysplastic. AML with multilineage dysplasia may develop after myelodysplastic syndromes or myelodysplastic/myeloproliferative neoplasms.

Therapy-related AML

This type of AML is related to previous chemotherapy with an alkylating drug or radiation therapy.

AML, not otherwise classified

This classification is used for AML that does not fall into one of the other categories. This group is classified in a similar way to the FAB system and includes:

• AML with minimal differentiation (FAB M0)
• AML without maturation (FAB M1)
• AML with maturation (FAB M2)
• acute myelomonocytic leukemia (AMML) (FAB M4)
• acute monocytic leukemia (FAB M5)
• acute erythroid leukemia (FAB M6)
• acute megakaryoblastic leukemia (FAB M7)
• acute basophilic leukemia (FAB M2Baso)
• acute panmyelosis with myelofibrosis
• chloroma (also known as extramedullary leukemia or granulocytic sarcoma or myeloid sarcoma)

FAB classification system

The FAB system is based mainly on how the leukemia cells, or blasts, look under the microscope. The AML is classified based on the type of cell from which the leukemia developed and how mature the cells are.

Unlike the WHO system, the FAB system does not include chromosome abnormalities.

Mixed phenotype acute leukemia

Sometimes the leukemia cells are considered mixed phenotype or mixed lineage because they have both myeloid and lymphoid characteristics. The leukemia cells may have both myeloid and lymphoid features on the same cell, or some leukemia cells have myeloid features and other leukemia cells have lymphoid features. Mixed phenotype acute leukemias (MPAL) are a special category of acute leukemias using the WHO classification system.

See a list of questions to ask your doctor about pathology and staging.