Not all gene mutations cause health issues, but some can affect the way blood cells develop. This can lead to acute myeloid leukemia (AML), which is a cancer of the blood.

This comes from the American Cancer Society.

In AML, the body produces too many white blood cells (WBCs). These WBCs are nonfunctioning and immature and crowd out healthy cells.

Genetics, as well as other factors, can help doctors determine the best treatments and shed light on a person’s outlook.

This article discusses how gene mutations can lead to AML, the different AML treatment options, and the prognosis for people with the condition.

A person studying acute myeloid leukemia gene mutation sheets.Share on Pinterest
Ted Horowitz/Getty Images

A genetic mutation is a permanent change in the DNA that makes up a gene. Experts also call these changes gene variants.

Not all gene variants cause disease, and not everyone with a variant that can cause health issues will necessarily develop a medical condition.

However, there are some gene variants that are risk factors for AML. A 2020 study lists six that experts have identified as potential risk factors:

  • FLT3
  • NPM1
  • RUNX1
  • ASXL3
  • TP53

There are many more gene mutations with links to leukemia development, and scientists are discovering more. Sometimes, these mutations occur in people with conditions that precede leukemia, such as myelodysplastic syndrome.

Researchers are not entirely certain about the cause of these gene mutations. Some believe they could be related to exposure to:

Genes hold all the information necessary for building and maintaining cells. When a cell divides into two new cells, it must make a new copy of its chromosomes for the new cell. Mistakes during this process can affect the genes within the chromosome, causing a gene mutation.

There are a couple of types of genes in charge of building and maintaining cells. They are oncogenes and tumor suppressor genes.

Oncogenes are mutated genes that, in their healthy state, help control when cells grow, divide, or die. When they mutate, they allow the cells to grow and divide uncontrollably.

Tumor suppressor genes control cell division or cause cells to die when they are supposed to.

Gene mutations that “turn on” oncogenes or “turn off” tumor suppressor genes can cause bone marrow cells, particularly immature WBCs, to grow out of control.

As these unhealthy cells continue to divide and grow, they develop into acute leukemia. The leukemic cells build up in the bone marrow and replace healthy cells, preventing the bone marrow from working properly.

Understanding a person’s AML type can help doctors determine the best treatment plan and potentially affect the person’s outlook.

Doctors classify AML in a few different ways.

The older French-American-British (FAB) classification divides AML into subtypes based on the type of cell from which the leukemia develops and the cell maturity.

The FAB subtypes are:

  • M0: undifferentiated acute myeloblastic leukemia
  • M1: acute myeloblastic leukemia with minimal maturation
  • M2: acute myeloblastic leukemia with maturation
  • M3: acute promyelocytic leukemia (APL)
  • M4: acute myelomonocytic leukemia
  • M4 eos: acute myelomonocytic leukemia with eosinophilia
  • M5: acute monocytic leukemia
  • M6: acute erythroid leukemia
  • M7: acute megakaryoblastic leukemia

A newer, more popular system comes from the World Health Organization (WHO). Its system divides AML into groups based on some of the factors researchers now know may affect the outlook.

The WHO groups are:

Undifferentiated and biphenotypic acute leukemias are not strictly AML, but they have some similar features. Doctors also refer to them as mixed-phenotype acute leukemias.

Additionally, some of the WHO groups have their own list of subtypes.

It is not possible to change the genes that may have contributed to the development of AML. For some, however, there are ways to suppress their activity.

Typically, there are two phases to AML treatment: remission induction and consolidation. During the remission induction phase, a person receives a drug or a combination of drugs to destroy as many leukemia cells as possible to reach AML remission.

Some people with gene mutations may receive an additional targeted therapy. For example, people with the FLT3 mutation may receive midostaurin (Rydapt), a twice-per-day oral medication that blocks FLT3 and other proteins that help cancer cells grow.

People with CD33-positive AML may receive gemtuzumab ozogamicin (Mylotarg) intravenously to deliver chemotherapy directly to the CD33 protein.

These are just a couple of instances in which a person might receive a targeted therapy along with standard chemotherapy for treating AML. As researchers highlight in a 2020 review, new gene mutation-targeted therapies are also in development.

Once a person reaches remission, they begin the consolidation phase. The goal here is to destroy any remaining cancer cells and prevent relapse.

Consolidation therapy might consist of:

Additionally, a person might continue with the targeted therapies from the induction phase, such as Rydapt.

Each AML consolidation treatment option has pros and cons. When determining the best treatment, a person’s doctor will weigh those pros and cons against factors such as:

  • how long it took to reach remission in the induction phase
  • donor stem cell availability
  • whether it is possible to collect cancer-free cells from the person’s bone marrow
  • prognostic factors, including favorable or unfavorable gene mutations
  • age and health

Regarding age and health, someone who is older or has other health issues might not be able to tolerate some of the more intensive therapies. When this is the case, a doctor may recommend:

  • different levels of cytarabine
  • a standard level of cytarabine along with other chemotherapy drugs, including idarubicin, daunorubicin, and mitoxantrone
  • lower doses of chemotherapy for a stem cell transplant

At any point before, during, or after AML treatment, people who wish to can consult their doctor about forgoing chemotherapy and other intensive AML treatments. Some people prefer instead to focus on supportive care that treats their symptoms and helps them stay comfortable.

Approximately 2 out of 3 people with AML who receive standard induction chemotherapy go into remission. For people older than 60, this number drops to around half the patients.

Statistics show that the 5-year survival rate during 2012–2018 was 30.5%. This means that close to one-third of AML patients survived for 5 years or more after their diagnosis.

However, gene mutations do affect this. People with changes in the NPM1 gene and no other mutations may have a better outlook, and so may people with mutations in both copies of the CEBPA gene.

However, people with mutations in the FLT3, TP53, RUNX1, and ASXL1 genes may have a poorer outlook than others.

Other factors that influence prognosis include:

  • Subtype: The AML subtype is an important factor. For instance, people with APL tend to have a more favorable prognosis than those with other subtypes. Approximately 9 out of 10 people with APL go into remission after standard induction therapy, and roughly 8 out of 10 of them will stay in remission with consolidation and maintenance therapy.
  • Chromosomes: Some chromosome abnormalities may affect a person’s AML prognosis. For instance, people with a translocation between chromosomes 8 and 21 typically have a favorable outlook. By contrast, people with chromosome 11 abnormalities may have an unfavorable outlook.
  • Other conditions: Having another blood condition, a blood infection at the time of diagnosis, or a history of cancer may affect the outlook.
  • Leukemia cells in the nervous system: If leukemic cells spread to the spinal cord or brain, this is more difficult to treat. Most chemotherapy drugs cannot reach these areas.

Gene mutations are common and do not always cause disease. Sometimes, however, gene mutations can lead to health issues. Several genetic variants are risk factors for AML, the most common of which is FLT3.

Genetic variants can influence a person’s treatment and outlook.

For some, it may be possible to try targeted drugs that suppress the activity of certain genes. People can ask a doctor about this and whether genetic mutations are a factor in their case.