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What Causes Acute Myeloid Leukemia?

Posted on May 11, 2021
Medically reviewed by
Todd Gersten, M.D.
Article written by
Jennifer Shuman

Acute myeloid leukemia (AML) — also known as acute myelogenous leukemia — is a type of cancer that begins in the bone marrow, where new red blood cells, white blood cells, and platelets are made. As AML progresses, leukemic (cancerous) cells build up and crowd out healthy blood cells. AML usually progresses quickly.

Symptoms of early stage AML are usually caused by a high proportion of immature cells — compared to normal, healthy cells — in the bone marrow and blood. Symptoms of AML are similar to the flu and can include:

  • Anemia
  • Bone pain
  • Easy bruising
  • Fatigue
  • Fever
  • Frequent infections
  • Loss of appetite
  • Pale skin
  • Shortness of breath
  • Unusual or frequent bleeding

Although the exact cause of AML is unknown, experts do understand risk factors for AML — as well as how the cancer develops.

How Healthy Cells Transform Into Cancerous Cells

AML results when cells are transformed into cancer cells in an abnormal bone-marrow environment. The dysfunctional cancerous cells eventually crowd out healthy, functional blood cells.

During normal cell growth and division, cells listen to signals that tell them when to grow, replicate their DNA, and divide into new cells. Cells become cancerous when they no longer respond to signals appropriately. Cancerous cells are always growing and dividing, despite there being no signal to do so — and even when a signal tells them to stop. This inability to listen to appropriate signals is due to mutations in the genes that control the progression of the cell’s cycle. When cells replicate quickly, there is a greater chance for errors to occur that lead to cancer.

This uncontrolled growth and division transforms the local bone-marrow environment into a niche that supports leukemia. The uncontrolled cell proliferation (growth), paired with the changed bone-marrow cells, encourages further disease progression.

Risk Factors for Acute Myeloid Leukemia

There are several known risk factors associated with the development of acute myeloid leukemia.

Genetic Mutations

Genetic changes have been identified in more than 97 percent of AML cases. There are several different types of mutations that can lead to overgrowth and division of AML cells.

Genes that put a pause on the normal cycle of cell growth and division are mutated in more than 30 percent of AML cases. In about 50 percent of AML cases, genes that help cells progress to the normal cycle of growth and division are mutated.

In about 40 percent of AML cases, mutations are present that do not affect the DNA but rather how and when DNA is read and expressed — called epigenetic changes. These changes cause a continuous, abnormal cycle of cell growth and division, even when signals to stop the cell cycle are present. Some epigenetic changes are reversible and may become targets for medication.

Sometimes, large pieces of DNA known as chromosomes break off and are rearranged, known as chromosomal translocations. Some chromosomal translocations result in abnormal proteins that are made up of parts of different proteins. This can lead to the formation of immature, abnormal cells that grow and divide too much.

Inherited vs. Acquired Mutations

These mutations can happen spontaneously over time (acquired mutations) or can be passed down from your parents (inherited mutations). AML usually does not run in families, and it often occurs suddenly in healthy people with no personal or family history of blood disorders. Scientists are still working to find out why some people suddenly develop leukemia.

Timing of Mutations

In 2018, researchers conducted a study involving more than 200 women who did not have AML at the time of enrollment but later developed the condition. The researchers found that associated genetic changes often occurred long before the participants had been diagnosed with the condition. They also found that several mutations significantly increased the risk of developing AML, years after the first genetic mutations were observed.

It is not known when certain mutations appear, how they happen, nor the specific risk associated with each gene. Some genes indicated a high risk for developing AML, however. Women who had TP53, IDH1, or IDH2 gene mutations later developed AML.

Age

The incidence of AML increases with age. More than 50 percent of people living with AML are older than 60. Genetic changes associated with AML naturally occur as part of the aging process. About 10 percent of people over the age of 65 have clonal hematopoiesis (a condition associated with increased risk of AML and heart disease, though few people with clonal hematopoiesis later develop AML). People living with AML who are elderly, have a sedentary lifestyle, and have other conditions are more likely to have severe AML.

Sex

According to Mayo Clinic, men are more likely to be diagnosed with AML than women.

Genetic Disorders

Some inherited and acquired disorders related to impaired bone-marrow function (such as bone marrow failure syndrome) are associated with a higher risk of AML development. Down syndrome and some other genetic disorders are also associated with the development of AML.

Environmental Factors

Prior exposure to radiation therapy or chemotherapy (which often happens during cancer treatment) has been linked to an increased risk of developing AML. So, too, has exposure to chemicals such as benzene. People are exposed to benzene and other dangerous, carcinogenic (cancer-causing) chemicals through cigarette smoke.

How To Lower the Risk of Developing Acute Myeloid Leukemia

In most cases, the cause of AML is unknown. Additionally, many of the risk factors for developing AML cannot be changed. There is no sure way to prevent the development of AML. The biggest controllable risk factor for AML development is smoking, and quitting smoking may reduce your risk.

Talk With Others Who Understand

MyLeukemiaTeam is the social network for people living with leukemia and their loved ones. On MyLeukemiaTeam, more than 8,200 members come together to ask questions, give advice, and share their stories with others who understand life with leukemia.

Are you living with leukemia? Does leukemia run in your family? Share your experience in the comments below, or start a conversation by posting on MyLeukemiaTeam.

Todd Gersten, M.D. is a hematologist-oncologist at the Florida Cancer Specialists & Research Institute in Wellington, Florida. Review provided by VeriMed Healthcare Network. Learn more about him here.
Jennifer Shuman is a graduate student at Vanderbilt University pursuing her Ph.D. in pathology, microbiology, and immunology. Learn more about her here.

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