Do We Know What Causes Chronic Lymphocytic Leukemia?

The exact cause of most cases of chronic lymphocytic leukemia (CLL) is not known. But scientists have learned a great deal about the differences between normal lymphocytes and CLL cells.

Normal human cells grow and function based on information in each cell's chromosomes. Chromosomes are long molecules of DNA. DNA is the chemical that carries our genes − the instructions for how our cells work. We look like our parents because they are the source of our DNA. But our genes affect more than the way we look.

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.

Some genes contain instructions for controlling when our cells grow and divide.

• Certain genes that promote cell growth and division are called oncogenes.
• Genes 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 mutations (changes) that turn on oncogenes or turn off tumor suppressor genes.

Each human cell contains 23 pairs of chromosomes. In most cases of CLL, a change can be found in at least one of these chromosomes. Most often this change is a deletion − that is, loss of part of a chromosome. The loss of part of chromosome 13 is the most common deletion, but other chromosomes such as 11 and 17 can also be affected. You might see this written as del(13q), del(11q), or del(17p). Sometimes there is an extra chromosome 12 (trisomy 12). Other, less common abnormalities may also be found. Scientists know these chromosome changes are important in CLL, but it's not yet clear which genes they involve or exactly how they lead to leukemia.

We do know that normal B lymphocytes are part of the immune system. They're programmed to grow and divide when they come into contact with a foreign substance called an antigen. (Scientists call substances foreign if they don't normally occur in a person's body and can be recognized by their immune system. Germs contain foreign antigens. So do blood cells from someone else with a different blood type.) Scientists think that CLL begins when B lymphocytes continue to divide without restraint after they have reacted to an antigen. But why this happens is not yet known.

Sometimes people inherit DNA mutations from a parent that greatly increase their risk of getting certain types of cancer. But inherited mutations rarely cause CLL. DNA changes related to CLL usually occur during the person's lifetime, rather than having been passed on from a parent.