AML is different from other cancers in that it does not generally grow in one spot to form a tumor. Instead, the abnormal leukemia cells enter from the bone marrow into the bloodstream and spread throughout the body. Because of this, AML has to be classified differently than other types of cancers. Specialists have created an AML classification system based on the different risk factors associated with the disease. The system currently most widely used is the 2016 World Health Organization (WHO) Classification of AML.
These classifications include:
- AML with genetic abnormalities: This classification includes abnormalities in the chromosomes of the leukemia cells.
- AML with myelodysplasia-related features: This is characterized by 20% or more leukemia cells or "blasts" found in the blood or bone marrow. It is also categorized by dysplasia or the abnormal distribution of cells throughout the body. This type of AML is primarily present in older patients.
- Therapy-related AML: This type is related to previous chemotherapy or radiation exposure. Treatments for cancers and autoimmune diseases that utilize chemotherapy and radiation therapy can cause AML.
- AML Not Otherwise Specified (NOS): This refers to AML that does not fit into any of the other categories
- Myeloid Sarcoma: This is when leukemia cells form a tumor mass outside of the bone marrow. This can happen around the bone structures of the skull, sinuses, sternum, ribs, vertebrae, pelvis and other parts of the body.
- AML associated with Down Syndrome: Children with Down Syndrome are 10-20 times more likely to develop leukemia. AML in these children is most common in those under the age of 3.
This classification system takes into account known causes and risk factors such as:
- White blood cell count
- A high white blood cell count at the time of diagnosis (this is linked to a more severe prognosis)
- Prior blood disorders or cancers
- Previous chemotherapy or radiotherapy for another cancer or disease
As more research on AML emerges, specialists now have more ways of evaluating and categorizing AML. We now know that AML is not a single disease but rather a disease of many types. The different types of AML depend on:
- How developed the leukemia cells are at the time of diagnosis
- The kinds of proteins present on the surface of the leukemia cells
- How different the leukemia cells appear to be when compared to normal cells
- The type of genetic abnormality the leukemia cells present
Doctors use genetic testing to evaluate the chromosomes (long strands of DNA) in the leukemia cells. Additional genetic tests also allow doctors to identify specific mutations a patient with AML may have in their leukemia cells. Identifying these changes and abnormalities can help doctors recognize and treat specific subtypes of AML.
Early recognition of these different subtypes can be vital to providing targeted care and therapy.
Mutations, which are genetic changes to specific genes, are found in many cases of AML and can lead to specific types of AML. These mutations allow abnormal cells to grow out of control. The specific type of genetic mutation a patient has can help determine if the AML is more or less aggressive as well as more or less likely to respond to certain treatments.
The most common genes that become mutated in AML include FLT3, IDH1, IDH2, NPM1, DNMT3A, CEBPA, TET2, and KIT. Drugs have been and are currently being developed to target these specific genetic mutations. This personalized medicine approach allows for the treatment of AML to be much more effective for many patients.
Four types of chromosomal changes can take place in AML. These changes help determine a patient's prognosis and what type of treatment should be given. Understanding what these chromosomal abnormalities mean and what their shorthands are can be vital in finding the right treatment:
- Inversion: When a section of a chromosome is flipped. Inv(16) is a type of inversion that may be found in AML. Abnormalities of chromosome 16 are found in about 5–8% of AML. Inv(16) is associated with a high rate of remission and favorable overall survival when treated with high doses of a drug called Cytarabine.
- Translocation: A section of one chromosome is taken and attached to another chromosome. Possible translocations in AML are: t(15;17), t(8;21) and t(16;16). The translocation t(15;17) is found in acute promyelocytic leukemia (APL), a subtype of AML which has a very different treatment than if a patient has a t(8;21) translocation.
- Deletion: A section of the chromosome is deleted and all the genes associated with that section are lost. Deletion of long arms of chromosomes 5 and 7, predicts a poor prognosis in AML.
- Duplication: A section in a chromosome appears twice which results in an excess of genetic material in the cell.
Acute Promyelocytic Leukemia (APL)
APL is the most common subtype of AML, and it is correlated with a more favorable prognosis. APL has a very specific treatment of vitamin therapy that is often effective. The mutation associated with APL is called a translocation, or a swapping of genes between two chromosomes, specifically between chromosomes 15 and 17. The shorthand for this mutation is t(15;17). “t” stands for translocation and (15;17) represents which chromosomes are being swapped. There are 23 pairs of chromosomes numbered 1-23 in human cells. See our APL page for more specific information.