Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML), a form of blood cancer. APL is an aggressive cancer, meaning it can grow and spread rapidly. Despite this, APL has high levels of remission.

APL is a relatively rare cancer, accounting for about 7–8% of adult AML cases. If a doctor suspects that a person has APL, they may start them on treatment immediately. Without treatment, APL can cause life threatening bleeding or blood clotting issues.

Read on to learn more about APL, including its symptoms, causes, and treatments.

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APL is a form of AML, a blood cancer that affects a person’s bone marrow. Bone marrow contains stem cells, which are cells that can develop into various other types of cells. Stem cells in the bone marrow develop into blood cells, such as:

  • red blood cells, which carry oxygen around the body
  • white blood cells, which help fight infections
  • platelets, which help form blood clots

If a person has APL, their bone marrow overproduces an underdeveloped form of white blood cells called a promyelocyte. These promyelocytes build up inside the bone marrow, leading to an underproduction of healthy white blood cells.

A person who has APL may experience various symptoms, including:

APL occurs due to a mutation in a person’s genes. Genes contain information that a person inherits from their parents. Some genes include information for the production of specific proteins.

The cells of the body contain chromosomes, which are long strands of DNA containing a person’s genes.

When a person has APL, the PML gene on chromosome 15 and the RARA gene on chromosome 17 swap genetic material. This process is known as translocation. During translocation, part of the PML gene fuses with part of the RARA gene. This fused gene creates the protein PML-RARα.

Usually, the protein that the PML gene produces helps prevent cells from dividing or growing too quickly. The protein that the RARA gene produces helps white blood cells mature past the promyelocyte stage.

The PML-RARα protein, however, interferes with the functions of both of these proteins. As a result, the promyelocytes cannot mature into white blood cells, and they multiply rapidly. Promyelocytes build up inside the bone marrow, which disrupts the production of healthy white blood cells.

Occasionally, translocation between the RARA gene and other genes can occur. However, PML-RARA gene fusions account for up to 98% of all APL cases.

Learn more about potential risk factors for developing AML.

Is APL hereditary?

No, a person cannot inherit APL. APL is the result of a somatic mutation. A somatic mutation is an abnormality that occurs in a person’s genes after conception and does not pass from parent to child.

APL can also occur as a result of previous cancer treatments. Radiation therapy and chemotherapy can cause a person to develop a form of APL called therapy-related APL. Therapy-related APL is especially likely if a person’s cancer treatment involves a type of medication called topoisomerase II inhibitors.

Learn about other types of leukemia and whether they are hereditary.

The treatment for APL is different than that for other forms of AML. Regular chemotherapy drugs kill promyelocytes, causing them to release proteins that lead to uncontrollable blood clotting and bleeding. This can lead to a person developing clotting or bleeding complications, potentially resulting in death.

According to the American Cancer Society, the treatment for APL usually involves three stages:

1. Induction

The aim of the induction stage is to reduce the number of APL cells, ultimately leading to remission. Remission is when there are no or very low levels of cancerous cells.

A drug called all-trans retinoic acid (ATRA) can help promyelocytes mature into white blood cells by eliminating the PML-RARα protein. As a stand-alone treatment, ATRA treatment can lead to remission in at least 80% of people with APL. However, additional treatment is required for remission to be long lasting.

ATRA treatment usually happens alongside one of the following:

  • arsenic trioxide (ATO), which doctors may administer with gemtuzumab ozogamicin for people with APL that is likely to return after treatment
  • chemotherapy with an anthracycline drug, such as daunorubicin or idarubicin, with the addition of cytarabine if the risk of relapse is high
  • chemotherapy and ATO treatment

Induction treatment generally continues until a person is in remission, which can take up to 2 months. A doctor may take a bone marrow biopsy after 1 month to check for remission.

Learn more about AML treatment.

2. Consolidation

Consolidation can help keep a person in remission from APL. It can also help remove any remaining APL cells. A person will generally receive the same drugs that they had during the induction phase. However, the dosage or timing of their treatment may change.

The consolidation phase usually takes several months depending on what treatment a person is taking.

3. Maintenance

If a person has a higher risk of their APL returning, they may require further treatment after consolidation. Maintenance therapy involves a person receiving lower dosages of drugs over a longer period.

The most common treatments for maintenance therapy are ATRA alone or ATRA with chemotherapy — either 6-mercaptopurine (6-MP), methotrexate, or both.

A person may continue maintenance therapy for up to a year.

If a person’s APL does not go away with treatment, they may choose to have a bone marrow transplant. A person may also receive supportive treatment for their APL symptoms.

A doctor can use certain tests to diagnose someone with APL. These tests include:

  • Bone marrow biopsies and blood tests: These look at the appearance and number of a person’s blood cells.
  • Karyotyping and fluorescence in situ hybridization (FISH) tests: These look at a person’s chromosomes.
  • Polymerase chain reaction (PCR) tests: These look for changes in the structure or function of a person’s genes.

Learn about bone marrow biopsies for AML.

Although APL is a form of AML, there are certain differences in the way that doctors treat it. Treatments for AML could cause life threatening complications for someone with APL. Doctors may treat AML using:

  • chemotherapy
  • surgery
  • radiation therapy
  • targeted drug therapy
  • stem cell transplants

Without treatment, bleeding and blood clotting issues due to APL can be life threatening. Additionally, certain side effects can develop due to APL treatment. These side effects include:

ATRA therapyATO therapy
headaches
fever
dry skin and mouth
rashes
swollen feet
sores in the mouth or throat
itching
irritated eyes
tiredness
nausea
vomiting
diarrhea
abdominal pain
numbness and tingling in the hands and feet
problems with heart rhythm

Differentiation syndrome

Both ATRA and ATO can cause differentiation syndrome. This side effect occurs when the leukemia cells release chemicals into the bloodstream, which can result in:

  • breathing problems
  • a buildup of fluid in the lungs, around the heart, and in other parts of the body
  • low blood pressure
  • kidney damage

Differentiation syndrome usually occurs in the first few weeks of APL treatment. It can also develop in people with high white blood cell numbers.

Information from 2021 notes that the 2-year APL-free survival rate for a person receiving ATRA-ATO therapy was 97%. The 2-year APL-free survival rate for a person treated with ATRA-chemotherapy was 90%.

However, without treatment, APL will generally result in death due to bleeding or infection-related complications. It is important that a person who has APL symptoms speak with their doctor immediately.

Acute promyelocytic leukemia is a form of AML that occurs due to a mutation in a person’s genes that causes a buildup of promyelocytes. This overproduction of promyelocytes leads to a reduction in healthy white blood cells.

APL responds well to treatment. However, without treatment, APL can lead to bleeding- and infection-related complications. A person who has APL symptoms should speak with their doctor urgently.