Do We Know What Causes Acute Myeloid Leukemia?
Some people with acute myeloid leukemia (AML) have one or more known risk factors (see “ What are the risk factors for acute myeloid leukemia?”), but many do not. Even when a person has one or more risk factors, there is no way to tell if it actually caused the cancer.
Scientists have learned how certain changes in DNA can cause normal bone marrow cells to become leukemia cells. Normal human cells grow and function based on the information contained in each cell’s chromosomes. Chromosomes are long strands of DNA in each cell. The DNA inside our cells makes up our genes – the instructions for how our cells function. We tend to look like our parents because they are the source of our DNA. But our genes affect more than how we look.
Some genes control when our cells grow, divide to make new cells, and die at the right time. Certain genes that help cells grow, divide, or live longer are called oncogenes. Others that slow down cell division or make cells 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 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 common in AML cells. These types of changes can help cells grow out of control.
Mutations in specific genes 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 to be due to changes in just one or a few genes that are on that part of the chromosome. 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 like RUNX1and RARa, which would normally help blood cells to mature.
- Deletions occur when part of a chromosome is lost. This can 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’s 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 or duplication 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.
Different cases of AML can have different chromosome changes, and some changes are more common than others. Doctors are trying to figure out why these changes occur and how each of them might lead to leukemia. For example, some are more common in leukemia that occurs after chemotherapy for another cancer.
Some changes 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 “ How is acute myeloid leukemia classified?”
Some people with certain types of cancer have inherited DNA mutations from a parent that increase their risk for the disease. Although this can happen in some cases of AML, such as in the genetic syndromes discussed in the “ What are the risk factors for acute myeloid leukemia?”, inherited mutations are not often a cause in AML.
Most DNA changes related to AML occur during a person’s lifetime, rather than having been inherited before birth. Some of these acquired changes may have outside causes like radiation or cancer-causing chemicals, but in most cases the reason they occur is not known. They seem to happen more often as we age, which might help explain why AML usually occurs in older people.
Last Medical Review: December 9, 2014 Last Revised: February 22, 2016