Diagnosing Acute Myeloid Leukemia (AML)
To diagnose leukemia, doctors perform a number of tests. Usually, doctors begin with a blood test (called a CBC, or complete blood count). Although the blood test may show leukemia cells, doctors need to examine a sample of bone marrow before confirming the exact diagnosis. This sample is obtained by performing a bone marrow aspirate, where doctors take a small amount of fluid from the bone marrow, where blood cells are made. Then they examine the fluid under a microscope to confirm the type of cancer before they begin treatment.
An additional test that may be performed along with the bone marrow aspirate is a bone marrow biopsy. A bone marrow biopsy may help in making a diagnosis when there are too few cells in the aspirate sample.
A spinal tap is usually performed to look for leukemia in the central nervous system. Following these tests, your doctor will ask the laboratory to perform cytogenetic tests (tests that check the leukemia’s chromosomes for mistakes, also called mutations). Not all chromosome mutations are easily found and sometimes they can only be seen using powerful laboratory techniques called molecular analysis (tests that look inside the chromosomes for extremely tiny mistakes). These tiny molecular mutations of the chromosomes may have a powerful impact upon the ability to be cured and have recently become the target of new medical treatments of leukemia. Based upon the chromosomal findings, your doctor can diagnosis the subtype of AML and can make an initial prognosis (prediction) for the chances of remission and long-term cure.
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Types of Acute Myeloid Leukemia
Acute Myeloid Leukemia can be divided into different subtypes which help your doctor determine both the general prognosis for cure as well as the best type of treatment.
Acute myeloid leukemia is caused by mutations in myeloid white blood cells. The body copies new white and red blood cells millions of times per day. In a normal person, a new blood cell (called a “blast”) will gradually develop (or “differentiate”) into a mature blood cell. In a cancer patient, a mutation during replication causes the blood cells to “freeze” in an early stage of development. For acute myeloid leukemia to develop, this mutation has to be combined with another mutation that disrupts how cells replicate, causing these immature blasts to multiply. There are several types of abnormalities in chromosomes that cause normal myeloid cells to become leukemia cells.
Recent advances have allowed doctors to pinpoint some of the specific mutations that cause different sub-types of acute myeloid leukemia. We now know that some of these mutations are low risk, and can be more easily cured. Other mutations are high risk, meaning these sub-types have higher rates of relapse and higher risk of treatment failure.
Risk Classification
Currently, among the many types of mutations that cause AML, there are only a few that are known to impact risk of treatment failure. These are grouped into low or high risk for treatment failure below. This grouping of risk types of AML comes from the Children’s Oncology Group’s research into AML therapy and is based upon the subtypes of AML defined by the World Health Organizations WHO 2008 Myeloid Classification publication. The names for these AML subtypes are either based upon the chromosome number on which the mutation can be found by cytogenetic testing or upon the specific gene mutations within the chromosomes found by molecular analysis.
Low-Risk AML Mutations
Cytogenetically Diagnosed Molecularly Diagnosed
Inversion 16 AML CEBPα AML
8;21 AML NPM (nucleophosmin) AML
High-Risk AML Mutations
Cytogenetically Diagnosed Molecularly Diagnosed
Monosomy 7 AML FLT3 high allelic ratio AML
Abnormal Chromosome 5q AML
Determining the Extent of Disease
Since AML is a cancer of the blood, it does not have “stages” the way solid tumors do. By nature, leukemia is widespread at diagnosis, but this does not affect successful treatment. However, leukemia cells can also be present in the spinal fluid, which is known as Central Nervous System (CNS) disease. Doctors will perform a special test known as a spinal tap or lumbar puncture to obtain fluid that they use to examine whether the disease has spread to the spinal fluid.
In addition to being present in the bone marrow and blood, AML can spread to areas that are part of the blood system, causing enlargement of the organs. It can affect many sites, but the most common are:
- Lymph nodes
- Liver
- Spleen
- Testes
- Skin
- Gums
Involvement of other organs other than the CNS usually has no bearing on the type of treatment given.
Causes of AML
We currently do not know what causes AML but certain factors increase the risk of developing AML. They include:
Genetic conditions: Children with some genetic syndromes are more likely than others to have their myeloid cells develop additional mutations that lead to AML. These are children with Down syndrome, Fanconi anemia, neurofibromatosis type 1, Bloom syndrome, Schwachman syndrome, familial monosomy 7 and Kostmann granulocytopenia. Children with these genetic conditions are more at risk for AML, but most children with AML do not have one of these conditions. These syndromes usually require medical care, so you would know if your child has one of them.
Ionizing radiation (x-rays): Early studies showed there was an increased risk when the baby was x-rayed while in its mother’s womb. Today, however, researchers believe that x-rays during pregnancy cause few if any cases of AML because pregnant women are not x-rayed often and the amount of radiation used in x-rays is much, much lower than it was years ago. Children who receive x-rays to diagnose a medical condition, such as a broken bone or tooth decay, are NOT at increased risk – much higher, cumulative, doses of radiation are required to cause AML.
Chemotherapy for a previous cancer: Treatment with certain chemotherapy medications increases the risk of AML, although the overall risk is low.
