Scientists still do not know exactly what causes most cases of multiple myeloma. However, they have made progress in understanding how certain changes in DNA can cause plasma cells to become cancerous. DNA is the chemical that carries the instructions for nearly everything our cells do. Some genes (parts of our DNA) contain instructions for controlling when our cells grow and divide. Certain genes that promote cell division are called oncogenes. Others that slow down cell division or cause cells to die at the appropriate time are called tumor suppressor genes. Cancers can be caused by mistakes, or defects, in the DNA called mutations that turn on oncogenes or turn off tumor suppressor genes.

Recent studies have found that abnormalities of some oncogenes (such as c-myc) develop early in the course of plasma cell tumors. Changes in other oncogenes (such as N-ras and K-ras) are more often found in myeloma after bone marrow relapse, and changes in tumor suppressor genes (such as p53) are associated with spread to other organs.

Myeloma cells also show abnormalities in their chromosomes. Normal human cells contain 46 chromosomes -- pieces of DNA and protein that control cell growth and metabolism. One fairly common finding in myeloma cells is that parts of chromosome number 13 are missing. These deletions appear to make the myeloma more aggressive and resistant to treatment.

About half of all people with myeloma have abnormally translocated chromosomes in their myeloma cells. This means that a part of one chromosome has switched with another part. This often occurs in a crucial area next to an oncogene, which causes it to be turned on.

Researchers have found that patients with plasma cell tumors have important abnormalities in other bone marrow cells and that these abnormalities may also cause excess plasma cell growth. Certain cells in the bone marrow called dendritic cells release a hormone called interleukin-6 (IL-6), which stimulates normal plasma cells to grow. Excess IL-6 production by these cells appears to be an important factor in development of plasma cell tumors.

Revised: 08/04/2006