Is Acute Myeloid Leukemia Hereditary?

If you or a family member has been diagnosed with acute myeloid leukemia (AML), you may be wondering if this cancer is genetic, or heritable. In most cases, leukemia is not hereditary and does not run in families.

Acute myeloid leukemia is a cancer of the blood cells. In the spongy tissue of the long bones (bone marrow), stem cells are constantly dividing and maturing into new blood cells. When cancer develops in the stem cells, it starts forming immature blood cells instead. These immature cells don’t work as well as mature blood cells.

About 20,000 new cases of AML were predicted to be diagnosed in the United States in 2021. In many of these cases, the patient either has no known risk factors or their main risk factors for AML are lifestyle and environmentally based, such as smoking and exposure to toxic chemicals.

But some AML patients inherit gene mutations that increase their risk of developing leukemia. AML also occurs more often in people with some inherited disorders such as ataxia telangiectasia (a rare disease that affects the nervous, immune, and body systems) and Down syndrome (trisomy 21, the presence of a third copy of chromosome 21). There is also a rare subtype of leukemia called familial AML that is passed through family lines. 

This article will review the main inherited risk factors for AML, including a rare familial subtype.

Risk Factors for Acute Myeloid Leukemia

Risk factors are anything that impacts the likelihood that you will develop a particular condition. Having a risk factor does not mean you will develop that disease. Not having a risk factor also doesn’t mean you won’t get the disease. 

Not all risk factors are made equal—some have a more significant impact on your risk of developing a condition than others. Some you can control (like smoking), while others are out of your grasp.

Genetics

Cancer develops when genes mutate within a specific cell over a person's lifetime, but genetics only plays a role in that mutation developing some of the time. Mutations in cancer cells that occur during your lifetime can't be passed down—they are not present in the eggs and sperm that give your genes to your biological children. 

Genetic changes that are inherited and directly cause or increase the risk of AML are rare. There is only one known rare subtype of AML that is caused directly by an inherited mutation. 

Family History 

Family history is a way of saying that a close relative has had the disease. A family history of a specific disease could mean that a sibling or parent has or had it. Having a family history of AML does increase your risk of developing it.

The family history factor could be due to various genetic changes that don’t directly cause AML but lead to increased risk. It could be due to shared environmental factors from living in a certain area or having a certain lifestyle. 

Demographics 

Some of the most important risk factors for AML are:

• Your age: Older adults are more at risk of developing AML.
• Your sex: Males are more at risk of AML than females.

Other Inherited Genetic Disorders

Several genetic conditions may increase the risk of AML, but they only play a small part in the number of patients diagnosed with this cancer every year — they are all quite rare. They include:

• Severe congenital neutropenia (also called Kostmann syndrome): A disorder showing very low white blood cell counts
• Ataxia telangiectasia: A disorder producing insufficient amounts of a protein that helps clear damaged cells, with symptoms of disordered movement and dilated blood vessels resulting in bloodshot eyes
• Bloom syndrome: A disorder with small stature, distinctive features, and sun sensitivity
• Down syndrome: An extra copy of chromosome 21 gives distinctive features and developmental and intellectual delays
• Fanconi anemia: A disorder with decreased production of all blood cell lines in the bone marrow
• Klinefelter's syndrome: A disorder in which a person has two X chromosomes and one Y chromosome (XXY)
• Li-Fraumeni syndrome: A disorder in which a mutation in a tumor suppressor gene gives increased risk of many types of cancer
• Neurofibromatosis type 1: A disorder in which tumors form around nerves
• Familial platelet disorder syndrome: A disorder that shows low platelet count and impaired platelet function and increased risk of blood disorders
• Wiskott-Aldrich syndrome: A disorder in which platelet count is low and immunity is impaired
  

Environmental Exposures

Some of the most significant risk factors for developing AML are your lifestyle and lifetime exposure to chemicals. These include:

• Smoking 
• Exposure to high levels of radiation (such as in survivors of nuclear bombs or reactor accidents or in people who had radiation treatment for cancer)
• Having undergone chemotherapy for another type of cancer or condition
• Exposure to chemicals such as benzene 

What Is Familial AML? 

One rare subtype of AML is due to an inherited genetic mutation in the gene CEBPA. The mutated CEBPA gene passes from parent to child and can cause a type of AML called familial acute myeloid leukemia.

The broken gene passes from parent to child through a dominant, non-sex-linked chromosome. So, if you have this mutation, you’ll have an increased risk of developing AML, and you will pass this risk on to your children. Luckily, only a few families harbor this extremely rare genetic mutation.

The familial subtype of AML leads to:

• Low white blood cell counts, called leukopenia, increasing the likelihood of infections
• Low red blood cell counts, leading to anemia (lack of healthy red blood cells), fatigue, and weakness
• Low platelet counts, leading to abnormal bleeding and bruising
• Fever and weight loss

This subtype of AML usually presents earlier in life than others, sometimes as early as childhood. Prognosis with familial AML is slightly better than AML as a whole.

About 50%–65% of those diagnosed with familial AML survive, while only 25%–40% of AML patients survive. However, familial AML is more likely to recur after successful treatment.

Coping and Support

If you or a family member is diagnosed with AML, you can be assured it is unlikely to be hereditary. However, you or your family will still need to come together to support the patient—many treatments for AML, including stem cell transplants, require support from others. 

If your AML is linked to a hereditary syndrome, ask your doctor about any other conditions you need to be aware of. Some hereditary leukemias can also increase your risk for other cancers, so vigilant care and regular screenings are important. 

Talk to your doctor about your syndrome and discuss with a genetic counselor the implications for other family members and your risk of recurrence after successful treatment. 

Summary 

AML is deadly cancer that most people develop due to random mutations or environmental exposures. In some rare cases, your risk for developing AML may be hereditary due to a genetic mutation or an underlying genetic syndrome. 

A Word From Verywell

When you develop a disease like AML, which often comes with a poor prognosis, it can be devastating to think that you may have passed on the risk to your family members. 

Unless your doctor mentions specific genetic conditions or familial subtypes of AML, it’s unlikely that you’ve inherited the disease or will pass it on. However, talk to a genetic counselor if you’re worried your children might be at risk of developing AML.