What Causes Multiple Myeloma?

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 make plasma cells 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. These genes that promote cell growth are called oncogenes.
• Others genes that slow down cell growth or make cells die at the right 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 MYC) develop early in the course of plasma cell tumors. Changes in other oncogenes (such as the RAS genes) are more often found in myeloma cells in the bone marrow after treatment, and changes in tumor suppressor genes (such as the gene for p53) are associated with spread to other organs.

Myeloma cells also show abnormalities in their chromosomes. In human cells, DNA is packaged into chromosomes. Although normal human cells contain 46 chromosomes, some cancer cells may have extra chromosomes (called a duplication) or have all or part of a chromosome missing (called a deletion). One common finding in myeloma cells is that parts of chromosome number 17 are missing. These deletions appear to make the myeloma more aggressive and resistant to treatment.

In about half of all people with myeloma, part of one chromosome has switched with part of another chromosome in the myeloma cells. This is called a translocation. When this occurs in a crucial area next to an oncogene, it can turn the oncogene 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. Excessive production of IL-6 by these cells appears to be an important factor in development of plasma cell tumors.