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The exact cause of most childhood leukemias is not known. Most children with leukemia do not have any known risk factors.

Still, scientists have learned that certain changes in the DNA inside normal bone marrow cells can cause them to grow out of control and become leukemia cells. DNA is the chemical in our cells that makes up our genes, which control how our cells function. We usually 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 into new cells, and die at the right time:

• Genes that help cells grow, divide, or stay alive are called oncogenes.
• Genes that help keep cell division under control or cause cells to die at the right time are called tumor suppressor genes.

Cancers can be caused by DNA mutations (or other types of changes) that keep oncogenes turned on, or that turn off tumor suppressor genes. These gene changes can be inherited from a parent (as is sometimes the case with childhood leukemias), or they may happen randomly during a person’s lifetime if cells in the body make mistakes as they divide to make new cells.

A common type of DNA change that can lead to leukemia is known as a chromosome translocation. Human DNA is packed into 23 pairs of chromosomes. In a translocation, DNA from one chromosome breaks off and becomes attached to a different chromosome. The point on the chromosome where the break occurs can affect oncogenes or tumor suppressor genes. For example, a translocation seen in nearly all cases of childhood chronic myeloid leukemia (CML) and in some cases of childhood acute lymphocytic leukemia (ALL) is a swap of DNA between chromosomes 9 and 22, which leads to what is known as the Philadelphia chromosome. This creates an oncogene known as BCR-ABL, which helps the leukemia cells grow. Many other changes in chromosomes or in specific genes have been found in childhood leukemias as well.

Inherited versus acquired gene mutations

Some children inherit DNA mutations from a parent that increase their risk for cancer (see Risk Factors for Childhood Leukemia). For instance, a condition called Li-Fraumeni syndrome, which results from an inherited mutation of the TP53 tumor suppressor gene, increases a person’s risk of developing leukemia, as well as some other cancers.

Certain inherited conditions can increase the risk of developing leukemia, but most childhood leukemias do not seem to be caused by inherited mutations. Usually, DNA mutations related to leukemia develop after conception rather than having been inherited. Some of these acquired mutations might occur early, even before birth. In rare cases, acquired mutations can result from exposure to radiation or cancer-causing chemicals, but most often they occur for no apparent reason.

Combinations of genetic and environmental factors

Some studies have suggested that many childhood leukemias may be caused by a combination of genetic and environmental factors. For example:

Certain genes normally control how our bodies break down and get rid of harmful chemicals. Some people have different versions of these genes that make them less effective. Children who inherit one of these gene changes may not be as able to break down harmful chemicals if they are exposed to them. The combination of genetics and exposure might increase their risk for leukemia.

Some research suggests that some childhood leukemias might be caused by a combination of certain gene changes that happen very early in life, along with being exposed to certain viruses later than normal. This “delayed infection” (after the first year or so of life) might affect the immune system in a way that leads to leukemia. For more on this, see What’s New in Childhood Leukemia Research?

Research on these and other possible causes of childhood leukemias is ongoing. But at this time the cause of most childhood leukemias is not known for sure. What's more, the different types of childhood leukemia might each have different causes.