Causes of acute myeloid leukaemia

The exact causes of acute myeloid leukaemia are unknown and in most cases it is unclear why leukaemia has developed. Research into possible causes is going on all the time.
Large doses of radiation may increase the risk of leukaemia. People exposed to high levels of radiation, such as nuclear industry accidents, have a higher risk of developing leukaemia than
people who have not been exposed to radiation.
Smoking increases the risk of developing AML. It is thought that this may be due to the concentrated levels of benzene in cigarette smoke. In very rare cases, AML may occur after longterm
exposure to benzene (and possibly other solvents) used in industry.

Rarely, some anti-cancer treatments such as chemotherapy or radiotherapy can cause leukaemia to develop some years later. The risk is increased when certain types of chemotherapy drugs are combined with radiotherapy. When leukaemia develops because of previous anti-cancer treatment this is called secondary leukaemia or treatment-related leukaemia.
People with certain blood disorders, such as myelodysplasia, or some genetic disorders, including Down's syndrome, have a higher risk of developing AML. It is not caused by an inherited faulty gene.
Acute myeloid leukaemia isn't infectious and can't be passed on to other people.
Symptoms of acute myeloid leukaemia
Most of the symptoms of acute myeloid leukaemia are due to the effects of the leukaemia cells in the bone marrow, which leave it unable to produce enough normal blood cells.
The main symptoms are:

Looking pale, feeling tired and breathless, which is due to anaemia caused by a lack of red blood cells.
Having more infections than usual, because of a lack of white blood cells.
Unusual bleeding, caused by too few platelets. This may include bruising easily without any obvious cause, bleeding gums, frequent nosebleeds, and heavy periods in women.
Some people have a rash of tiny, flat red spots on the skin of the legs or in the mouth. These are called petechiae.
Feeling generally unwell and run down.
Having a fever and sweats. This may be due to an infection or to the leukaemia itself.

Other, less common, symptoms may be caused by a build up of leukaemia cells in a particular area of the body, such as:

Aching bones, caused by pressure from a build up of immature cells in the bone marrow.
Raised bluish-purple areas under the skin - due to leukaemia cells in the skin.
Swollen gums, caused by leukaemia cells in the gums.

Occasionally, a person has no symptoms and the leukaemia is discovered during a routine blood test.
The symptoms of acute myeloid leukaemia may appear over a few weeks, and people often feel ill quite quickly. Treatment needs to be given as soon as possible. If you have any of the above symptoms you should have them checked by your doctor - but remember, they are common to many illnesses other than leukaemia.
How AML is diagnosed
Usually you will see your GP. They will examine you and take a blood test. If the results of the test are abnormal, your GP will refer you to hospital for advice and treatment from a doctor who
specialises in the treatment of blood problems (a haematologist).

At the hospital
Bone marrow sample/biopsy
Other tests

At the hospital

Most people with AML are referred for treatment at a haematology unit, where a group of specialist doctors work together. This is known as a multidisciplinary team and normally includes:

one or more haematologists
a clinical oncologist (a doctor who specialises in radiotherapy and chemotherapy)
specialist nurses who give information and support
pathologists who advise on the type and extent of the leukaemia.

Other staff will be available to help you if necessary, such as:

social workers
dietitians
counsellors and psychologists
physiotherapists.

The doctor at the hospital will ask you questions about your health and about any previous illnesses you have had. They will also examine you to find out how you are physically. You will have a blood sample taken to check the numbers of all the different types of blood cell in your blood (a full blood count).
If the blood test shows that leukaemia cells are present, your doctor will want to take a sample of your bone marrow. This is an important test for finding out about the leukaemia. It gives the
doctors information to help them plan the best treatment for you.
Bone marrow sample/biopsy
A small sample of bone marrow is usually taken from the back of your hipbone (pelvis). The sample is looked at under a microscope by a pathologist, who will identify the type of leukaemia. They will also count the number of immature blood cells (blasts) in the sample. Other tests will also be carried out on the bone marrow sample to help confirm the diagnosis.
The bone marrow sample is taken under a local anaesthetic. You will be given a small injection to numb the area and the doctor will gently pass a needle through the skin into the bone. The doctor will draw a small sample of liquid marrow into a syringe to be looked at later under the microscope (bone marrow aspirate). The doctor will then take a small core of marrow from the bone (a trephine biopsy).

A sample of bone marrow is usually taken from the back of the hipbone
The test can be done on the ward or in the outpatients department. The whole procedure takes about 15-20 minutes. It may be uncomfortable as the marrow is drawn into the syringe but this should only last for a few seconds. You may be offered a short-acting sedative to reduce any pain or discomfort during the test. You may feel bruised after the test and have an ache for a few days. This can be eased with mild painkillers.
Other tests
Your doctor may arrange for you to have other tests to check that your lungs, heart, liver and kidneys are healthy.
Classification of acute myeloid leukaemia

Why AML is classified
Cytogenetics
WHO and FAB classification of AML

Why AML is classified

Acute myeloid leukaemia (AML) can be divided up (or classified) into various sub-types. This is important as not all types of AML are treated in the same way. Your doctors need to know which type of AML you have to help them plan the most appropriate treatment for you.
Your bone marrow sample will be tested to find out which sub-type of AML you have. Tests that may be done include:

Examining the leukaemia cells under the microscope - to see what type of blood cell has become abnormal and at what stage of its development.
Testing leukaemia cells with antibodies to look for specific proteins on their surface. This is called immunocytochemistry, and also helps doctors to identify what type of cell has become abnormal.
Looking for particular types of changes in the chromosomes of leukaemia cells. This is called cytogenetics. It can help doctors to predict how well the leukaemia may respond to treatment.

Cytogenetics
Almost all the cells in our body contain chromosomes. Chromosomes are made up of genes, which control the activities of the cell. There are often changes in the structure of the chromosomes in leukaemia cells. A test on the bone marrow sample, called a cytogenetic test, looks for these changes.
Different types of AML are associated with particular genetic changes. So these tests can help doctors to decide on the best treatment and predict how well the leukaemia may respond to it.
WHO and FAB classification of AML
In the UK, doctors usually classify AML according to the World Health Organisation (WHO) system and the French American British (FAB) system. The WHO system classifies AML according to the type of cell that has become abnormal and whether:

there are particular chromosomal changes (cytogenetics)
there are abnormal changes in more than one type of blood cell
the leukaemia has developed from a previous blood disorder called myelodysplasia
the leukaemia is related to previous cancer treatment (treatment-related AML).

This system is important as it is useful for planning treatment and predicting response.
The FAB system looks at the appearance of the leukaemia cells under a microscope (morphology). Each type of AML is named according to the cell type and given a number from M0
to M7.
Doctors may classify AML with the FAB system while waiting for the results of other tests.