Acute promyelocytic leukemia (APL) is a type of acute myeloid leukemia (AML). With proper treatment, the survival rates are high.

APL is a relatively rare cancer, accounting for about 7–8% of adult AML cases. It is a form of blood cancer that involves high levels of immature white blood cells. APL can grow and spread rapidly but has high levels of remission. 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 or leukemia 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 known as promyelocytes. These promyelocytes build up inside the bone marrow, leading to an underproduction of healthy white blood cells.

Is leukemia the same as bone marrow cancer?

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

What do leukemia rashes and bruising look like?

APL happens when the bone marrow starts releasing cancerous or immature white blood cells into the blood and bone marrow. This buildup disrupts the production of healthy white blood cells.

It results from a change in 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. When this happens, 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.

PML-RARA gene fusions account for up to 98% of all APL cases. The remaining cases are due to other genetic changes involving RARA.

Learn more about potential risk factors for developing AML here.

Is APL hereditary?

No, a person cannot inherit APL, which is the result of a somatic mutation. A somatic mutation is a change 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 known as therapy-related APL. This is especially likely if a person’s cancer treatment involves the medication topoisomerase II inhibitors.

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

The treatment for APL is different from 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 make a person develop 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 induction stage aims to reduce the number of APL cells, ultimately leading to remission. Remission is when there are no or very low levels of cancerous cells.

The drug 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 8 in 10 people with APL. However, additional treatment is required for remission to be long-lasting.

ATRA treatment usually happens alongside one of the following treatments:

  • 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 here.

2. Consolidation

Consolidation can help keep a person in remission from APL. It may 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 need further treatment after consolidation. In maintenance therapy, a person receives 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 the following:

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

Learn about bone marrow biopsies for AML here.

Although APL is a form of AML, there are certain differences in the way that doctors treat it. Treatments for AML can 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.

It 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.

In the past, people with APL were unlikely to survive more than 1 month after diagnosis due to bleeding or an infection.

However, modern treatment has changed this, and doctors now consider APL highly curable.

Information from 2021 noted 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 receiving 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.

The survival rate refers to the proportion of people who are still alive for a length of time after receiving a particular diagnosis. For example, a 5-year survival rate of 50% means that 50%, or half, of people are still alive 5 years after receiving the diagnosis.

It is important to remember that these figures are estimates on the basis of the results of previous studies or treatments. A person can consult a healthcare professional about how their condition is going to affect them.

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Here are some questions people often ask about APL.

What is the survival rate for APL?

Research suggests that people who receive ATRA-ATO therapy for APL have a 97% chance of surviving at least another 2 years after diagnosis, compared with people who do not have APL. People who receive ATRA-chemotherapy have a 90% chance of surviving another 2 years.

How do you get APL?

APL results from genetic changes that happen after a person is born. It is not hereditary. Experts do not know what causes these changes, but chemotherapy, exposure to workplace toxins, and radiation are known risk factors.

What are the signs and symptoms of APL?

A person may experience:

  • weakness
  • fatigue
  • bleeding from the gums or nose
  • a rash or bruising, known as petechiae or ecchymoses
  • retinal hemorrhages that affect vision
  • heavy menstrual bleeding
  • infections
  • in some cases, a severe cardiovascular event, such as deep vein thrombosis, a pulmonary embolism, or a stroke

What are the symptoms of leukemia?

APL is a blood cancer and a form of AML. It happens when a genetic change causes a buildup of promyelocytes, which are immature or cancerous white blood cells.

The promyelocytes crowd out healthy blood cells, increasing the risk of bleeding problems, anemia, and infections.

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.