Do we know what causes childhood leukemia?

The exact cause of most cases of childhood leukemia is not known. Doctors have found that the risk of this cancer is increased in a number of genetic conditions, which are described in the section "What are the risk factors for childhood leukemia?" But it is important to note that most children with leukemia do not have any known risk factors.

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 strands of DNA in each cell. DNA is the chemical that makes up our genes – the instructions for how our cells function. We usually look like our parents because they are the source of our DNA. But our genes affect more than the way we look.

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

Cancers can be caused by DNA changes (mutations) that turn on oncogenes or 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 spontaneously during a person's lifetime if cells in the body make mistakes as they divide to form 2 new cells.

A common type of DNA abnormality that can lead to leukemia is known as a translocation. Human DNA is packaged in 23 pairs of chromosomes. A translocation means that DNA from one chromosome breaks off and becomes attached to a different chromosome. The point at which 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 swapping 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. Many other changes in chromosomes or in specific genes have been found in childhood leukemias as well.

Some children inherit DNA mutations from a parent that may increase their risk for cancer. 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 diseases can increase the risk of developing leukemia, but most cases of childhood leukemia 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 may occur early, even before birth. In rare cases, acquired mutations may result from exposure to radiation or cancer-causing chemicals, but usually they occur for no apparent reason.

A few studies have suggested that some 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 these genes 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.