Do we know what causes acute myeloid leukemia?

Some people with acute myeloid leukemia (AML) have one or more known risk factors (see the section called "What are the risk factors for acute myeloid leukemia?"), but most do not. The cause of their cancer remains unknown at this time. Even when a person has one or more risk factors, there is no way to tell whether it actually caused the cancer.

During the past few years, scientists have made great progress in understanding how certain changes in DNA can cause normal bone marrow cells to become leukemia cells. Normal human cells grow and function based mainly on the information contained in each cell's chromosomes. Chromosomes are long molecules of DNA in each cell. DNA is the chemical that makes up our genes -- the instructions for how our cells function. We resemble our parents because they are the source of our DNA. But our genes affect more than the way we look.

Some genes contain instructions for controlling when our cells grow and divide. Certain genes that promote cell division are called oncogenes. Others that slow down cell division or cause cells to die at the right time are called tumor suppressor genes.

Each time a cell prepares to divide into 2 new cells, it must make a new copy of the DNA in its chromosomes. This process is not perfect, and errors can occur that may affect genes within the DNA. Cancers can be caused by DNA mutations (changes) that turn on oncogenes or turn off tumor suppressor genes. For instance, changes in certain genes such as FLT3, c-KIT, and RAS are commonly found in AML cells.

Mutations in a single gene are found in many cases of AML, but larger changes in one or more chromosomes are also common. Even though these changes involve larger pieces of DNA, their effects are still likely due to changes in just one or a few genes. Several types of chromosome changes may be found in AML cells:

• Translocations are the most common type of DNA change that can lead to leukemia. A translocation means that a part of one chromosome breaks off and becomes attached to a different chromosome. The point at which the break occurs can affect nearby genes -- for example, it can turn on oncogenes or turn off genes that would normally help a cell to mature.
• Deletions occur when part of a chromosome is lost. This may result in the cell losing a gene that helped keep its growth in check (a tumor suppressor gene).
• Inversions occur when part of a chromosome gets turned around, so it is now in reverse order. This can result in the loss of a gene (or genes) because the cell can no longer read its instructions (much like trying to read a book backwards).
• Addition means that there is an extra chromosome or part of a chromosome. This can lead to too many copies of certain genes within the cell. This can be a problem if one or more of these genes are oncogenes.

Doctors are trying to figure out why these changes occur and how each of them might lead to leukemia. Not all cases of AML have the same chromosome changes. Some changes are more common than others, and some seem to have more of an effect on a person's prognosis (outlook) than others. For instance, they may affect how quickly the leukemia cells grow, or how likely they are to respond to treatment. This is discussed in more detail in the section called "How is acute myeloid leukemia classified?"

Some people with certain types of cancer have inherited DNA mutations from a parent. These changes increase their risk for the disease. But AML is very rarely caused by one of these inherited mutations.

Most DNA mutations related to AML occur during a person's lifetime, rather than having been inherited before birth. They may result from exposure to radiation or cancer-causing chemicals, but in most cases the reason they occur is not known.