Waldenstrom Macroglobulinemia

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Causes, Risk Factors, and Prevention TOPICS

Do we know what causes Waldenstrom macroglobulinemia?

Scientists have made great progress in understanding how certain changes in the DNA inside normal lymphocytes can cause them to become lymphoma or multiple myeloma cells. Changes in the DNA of some lymphoma cells can also cause them to make high levels of IgM, which leads to most of the symptoms of Waldenstrom macroglobulinemia (WM).

DNA is the chemical inside cells that carries the instructions for nearly everything they do. We tend to look like our parents because they are the source of our DNA. But DNA affects more than the way we look.

Our DNA includes genes that contain instructions for controlling when cells grow and divide to make new cells. 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 mutations (changes) that turn on oncogenes or turn off tumor suppressor genes.

Some people with certain types of cancer have DNA changes they inherit from a parent that increase their risk for the disease. Researchers are studying families that have many cases of WM to try to find the genes that may cause this disorder in some people.

The DNA changes found in WM cells are usually acquired after birth (not passed on from a parent). Acquired changes may result from exposure to something in the environment, such as radiation or cancer-causing chemicals. But often these changes occur for no apparent reason.

Recent research has found that about 9 times out of 10, WM cells have a mutation in a gene known as MYD88, which normally helps immune system cells signal each other and helps keep them alive. The change in DNA might cause the gene to stay turned on all the time, which might help the WM cells survive longer than they should.

Human DNA is packaged in 23 pairs of chromosomes. Sometimes, a piece of a chromosome is missing. This is called a deletion. The most common chromosome defect seen in WM is a deletion of part of chromosome 6. It’s not clear exactly which genes this might affect. Another type of chromosome defect in WM is called a translocation. In a translocation, a piece of one chromosome becomes attached to a different chromosome. Chromosome changes like these can cause oncogenes to be turned on or tumor suppressor genes turned off.

Researchers have found that some patients with WM have important changes or defects in other bone marrow cells. These changes may also help cancer cells grow. Certain cells in the bone marrow called dendritic cells release a hormone called interleukin-6 (IL-6) that helps normal plasma cells and plasmacytoid lymphocytes grow. Excess IL-6 production by these cells appears to be an important factor in the development of WM.

Last Medical Review: 06/19/2013
Last Revised: 06/19/2013