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
Without treatment, APL
Read on to learn more about APL, including its symptoms, causes, and treatments.
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.
A person who has APL may experience various symptoms, including:
- a pale complexion due to anemia, which may not be apparent in people with darker skin
- signs of bleeding due to low platelet levels, such as bruising, prolonged bleeding, or petechiae, which are tiny discolored spots on the skin
- tiredness
- mild fever
- swollen or bleeding gums
- frequent infections
- loss of appetite
- unexplained weight loss
- discomfort in the bones or joints
- an enlarged spleen
- an enlarged liver
- neurological symptoms, such as headaches, confusion, or visual changes
- nosebleeds
- blood in the urine
- excessive menstrual bleeding
- slow healing from injuries
APL
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.
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.
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
According to the
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. 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
3. Maintenance
If a person has a higher risk of their APL returning, they may need
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.
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
- 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
| ATRA therapy | ATO 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.
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.
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
How do you get APL?
APL results from genetic changes that happen after a person is born. It is not hereditary. Experts
What are the signs and symptoms of APL?
A person may
- 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
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.