Myeloma is a form of blood cancer that arises from plasma cells, the immune cells made in the bone marrow that are responsible for antibody production. In patients, these cells are abnormal and multiply out of control, increasing from about 1% of bone marrow cells to a majority of them.
While the exact cause of most myeloma cases remains unclear, scientists believe that genetic changes make plasma cells turn malignant, generating the so-called myeloma cells. The mutations that cause myeloma differ from person to person, and while some have been identified as genetic risk factors, the disease is not thought to be inherited.
Several mutations in oncogenes and tumor suppressor genes have been identified in myeloma cells. Oncogenes are genes that promote cell growth, while tumor suppressing genes are responsible for controlling or suppressing cell growth and triggering cell death when cells are dividing abnormally.
Mutations that either turn on oncogenes or turn off tumor suppressing genes have the potential to make cells grow out of control and survive beyond their normal lifespan.
Genetic changes in the MYC oncogene have been identified early in the course of the disease, while those in the RAS oncogenes are more often found in myeloma cells after treatment. Mutations in tumor suppressing genes such as p53 have been associated with the cancer’s spread to organs outside the bone marrow.
Most myeloma patients have duplications, deletions, or loss of genetic material, as well as abnormal exchanges of genetic material between chromosomes (called translocations). In translocations, chromosome segments and their genes change positions within the same chromosome or into another chromosome.
A common finding in myeloma cells is that parts of chromosome 17 are missing, and these deletions appear to be associated with a more aggressive and treatment-resistant cancer. Chromosome 1 deletions, duplications, and translocations have also been reported. Some patients also show deletions in chromosome 13.
Translocations in myeloma cells most often involve an exchange between chromosome 14 and another chromosome, such as 4, 6, 11, 16, or 20.
These chromosomal alterations may lead to changes in gene activity that drive the abnormal growth of plasma cells, such as those switching on an oncogene or switching off a tumor suppressor gene.
Notably, plasma cells mature from a type of immune cell called B-cells, and they may be more prone to mutations because B-cells undergo genetic rearrangements — involving DNA breaks and fusions — during development to build a wide selection of different antibodies.
Demographic factors associated with an increased risk of developing myeloma include older age — with most cases being diagnosed after age 65, male sex (males having a slightly higher risk than females), and Black race, which is associated with a twofold increased risk and a younger disease onset relative to whites.
People with a history of myeloma in the family or a personal history of other plasma cell-related conditions, such as monoclonal gammopathy of undetermined significance or solitary plasmacytoma, are more likely to develop the disease than those without these conditions.
In addition, obesity and exposure to high levels of radiation or to certain chemicals — such as asbestos and benzene (found in gasoline), and some pesticides and herbicides — have also been linked to a higher risk of myeloma.
Last updated: Dec. 10, 2021
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