Causes and Risk Factors of Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is caused by a genetic mutation in a person's DNA. In AML, this mutation involves the stem cells in bone marrow, where red and white blood cells and platelets are made. The disordered white blood cells, which would normally fight infections, are too immature to do so. As the number of cells with the mutation increases, they crowd out healthy blood cells, causing levels to fall.

Read on to learn more about the common causes, genetic influences, and lifestyle risk factors for acute myeloid leukemia.

Common Causes

While acute myeloid leukemia may run in families in rare instances, there seem to be other factors at play in most cases. Some common factors that put people at increased risk of developing the condition include:

• You are in an older age bracket.
• You have prior courses of chemotherapy or exposure to large doses of radiation, which can lead to cell mutations. Prior treatment for conditions such as childhood acute lymphocytic leukemia (ALL), Hodgkin disease, non-Hodgkin lymphoma, ovarian cancer, and breast cancer have all been linked to the development of acute myeloid leukemia.
• You have an immediate family member with the condition. This can put individuals at a two-fold to four-fold heightened risk of developing leukemia.
• You have a genetic condition such as Down syndrome or Fanconi anemia.
• You are male, which increases the risk for some unknown reason.
• You have a blood disorder such as polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis.

Genetics

With acute myeloid leukemia, certain DNA changes occur in otherwise normal bone marrow cells. It is up to your genes to instruct your cells when to divide and multiply and when to die.

Those genes responsible for cells dividing properly and remaining alive are known as oncogenes. Those responsible for cells dying off are known as tumor suppressor genes. Every time the cells divide, the strands of DNA inside must make copies and form chromosomes. This does not always go perfectly.

In acute myeloid leukemia, there often can be errors in those genes that switch off tumor suppressor genes or switch on oncogenes. NPM1 mutations are found in about 30% of all AML and 50% to 60% of AML with a normal karyotype (number and appearance of chromosomes), making it the most common genetic mutation in AML.

NPM1 rarely occurs with any of the recurrent genetic abnormalities (BCOR, or CEBPA) but frequently coexists with FLT3, DNMT3A, and IDH.

Changes in these can mean that the bone marrow cells may begin to proliferate wildly or not mature the way they should. With many different types of acute myeloid leukemia, some other genes and chromosomes can be affected.

It's not yet fully understood why these changes occur and may result in causing acute myeloid leukemia. In some cases, individuals may be at increased risk for this condition due to inherited factors, but this tends to be the exception and not the rule.

More likely, these tend to be related to risk factors such as radiation exposure or handling of cancer-causing chemicals. Still, no specific cause can be identified in many cases, with these appearing to be random events.

Lifestyle Risk Factors

In addition to genetic factors, which individuals have no control over, lifestyle factors can also play an important role. Lifestyle factors that can tip the balance toward developing acute myeloid leukemia can include:

• Smoking: Even though this condition is not related to the lungs, cancer-causing substances in tobacco can be released into the body by smoking. This is currently the only risk factor that has been verified. It's estimated that smoking accounts for about 20% of acute myeloid leukemia cases.
• Working with certain chemicals: Anyone who works in industries such as at chemical plants, in shoe manufacturing, in rubber plants, around motor vehicle exhaust, at oil refineries, or in gasoline-related industries may have long-term exposure to benzene, which can predispose them to this condition.
• Undergoing imaging tests involving low radiation levels: Especially if done early in life or when a person is pregnant, this can potentially put people at increased risk of acute myeloid leukemia. While the risk is likely small, it's important to limit exposure as much as possible.
• Being close to electromagnetic fields: While not proven, constant exposure to these fields, such as living near power lines, is thought to be possibly linked to acute myeloid leukemia development.
• Working with pesticides or herbicides: Exposure to these may also potentially make individuals vulnerable here. But this idea remains controversial.

Summary

Acute myeloid leukemia occurs when there are mutations in the DNA of the cells that normally produce some types of white blood cells. They grow out of control and crowd out normal cells in the bone marrow. Risk factors include age, sex, and exposure to radiation or chemotherapy.

Some genetic factors are also associated with AML. Smoking is a confirmed lifestyle risk factor. Possible risk factors include exposure to chemicals.

A Word From Verywell

While it would be great to pinpoint a cause for this condition in all cases, that is not possible at this point. Still, knowing some of the triggers here does offer some important control over the situation.

Knowing what factors have been linked and what can put you at risk for acute myeloid leukemia may help avoid developing it. Going forward, the hope is that as more is discovered about this condition, it will become possible for additional individuals to avoid this condition before it begins.