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 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 growth and 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.

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 some cases of childhood ALL is known as the Philadelphia chromosome, which is a swapping of DNA between chromosomes 9 and 22. 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, which increases their risk for cancer. For instance, a condition called Li-Fraumeni syndrome, which results from an inherited mutation of the p53 tumor suppressor gene, increases a person's risk of developing leukemia, as well as bone and soft tissue sarcomas and some other cancers.

But while certain inherited diseases can increase the risk of developing leukemia, 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.

Last Medical Review: 08/19/2007
Last Revised: 05/14/2009