Multiple myeloma falls into the general category of hematologic (blood) cancers. Blood cancers primarily affect the blood, bone marrow and lymph nodes, changing the production of blood cells and the way that they work. Myeloma affects the plasma cells found inside the bone marrow where blood is made. Myeloma cells develop when normal plasma cells transform and grow uncontrollably. As these abnormal cells multiply, they suppress the growth of healthy cells in the bone marrow. Because plasma cells are a part of the body’s immune system, this unusual cell growth can affect the body’s ability to fight infection and can result in anemia, bone damage and excessive bleeding from cuts.
Understanding bone marrow and cells
To fully understand multiple myeloma, it’s important to first gain a general knowledge of bone marrow and blood cells.
Bone marrow is the soft, spongy center of some bones that contains immature blood stem cells, more mature blood-forming cells, fat cells and tissues that support cell growth. The immature blood stem cells, known as hematopoietic stem cells, develop into several types of blood cells, including white blood cells, red blood cells and platelets (see Figure 1).
Lymphocytes are the primary cells in lymphoid tissue, which is a major part of the immune system. These cells develop from lymphoblasts (immature cells found in bone marrow) into mature, infection-fighting cells. Subtypes of these cells include B lymphocytes and T lymphocytes.
Plasma cells develop from B lymphocytes and produce antibodies to help fight germs and viruses and stop infection and disease. Plasma cells are primarily found in the bone marrow.
Antibodies are proteins created from plasma cells as a reaction to a foreign substance, such as bacteria, in the body.
Each plasma cell in your body makes antibodies for one specific substance. These antibodies are created when the plasma cells encounter a perceived threat to the body. For instance, if you catch a cold, plasma cells create antibodies that target the specific germs that are the cause of the illness. Your body has many types of plasma cells, and it can create antibodies to protect itself against many types of bacteria and disease.
Abnormal, cancerous plasma cells are called myeloma cells, and like normal plasma cells, myeloma cells make antibodies. But because myeloma cells are all the same, they produce too much of the same antibody. These antibodies are called monoclonal antibody proteins, or M proteins. M proteins accumulate in the blood and urine and can lead to damage of the kidneys or other organs.
In people with multiple myeloma, the myeloma cells multiply uncontrollably (see Figure 3). Over time, the myeloma cells accumulate in bone marrow, solid parts of bone and, occasionally, in other organs. When the cells collect in bone marrow, they slow down the growth of healthy white blood cells, red blood cells and platelets (see Figure 2). When these cells collect in solid bone, they cause holes called lytic lesions. The majority of people with multiple myeloma have these lesions when their disease is diagnosed.
Although scientists continue to learn more about how multiple myeloma develops, the exact cause of this disease is unknown. Research suggests that your risk for multiple myeloma can increase because of some factors, including a family history of multiple myeloma, exposure to certain chemicals and radiation, obesity and other plasma cell diseases such as monoclonal gammopathy of undetermined significance (MGUS).
Age, gender and race also play a role. Multiple myeloma is far more common in adults older than 60 to 65 years than in adults younger than 45, is more common in men than in women, and develops more often in African-American individuals than in Caucasian individuals.
Studies have also found that most people with multiple myeloma have identifiable genetic mutations in their plasma cells. For example, in about half of people with the disease, part of one chromosome in the myeloma cells has switched with part of another chromosome. Another common finding is that certain parts of one chromosome — chromosome 13 — are missing from these cells. Research is ongoing to determine the precise role these changes in DNA play in the cause of multiple myeloma.
Although scientists have discovered patterns between certain risk factors and the development of multiple myeloma, there is no solid evidence that these risk factors cause the disease.
Related plasma cell disorders
As mentioned previously, plasma cells are immune cells that create antibodies, which help fight infections. However, the following plasma cell disorders can result when the body makes abnormal plasma cells in excess amounts:
Monoclonal gammopathy of undetermined significance
MGUS is a condition that occurs when abnormal plasma cells begin to produce many copies of an identical antibody (see MGUS). These plasma cells do not usually form a mass or tumor, and MGUS will not usually affect a person’s health. Patients with MGUS do not require treatment, but the disease is closely monitored, as it can be a precursor to multiple myeloma. Although people with multiple myeloma have a monoclonal gammopathy, not all people with monoclonal gammopathy have multiple myeloma.
Plasmacytoma is a type of malignant, abnormal plasma cell growth that develops primarily in the bone but may begin in other tissues or organs. It is basically a solid tumor of myeloma cells that invades and overwhelms the healthy cells in the bone marrow as well as other parts of the body. People with a solitary plasmacytoma are at an increased risk for the development of multiple myeloma.
Amyloidosis is caused by a buildup of amyloid, an abnormal protein that can be produced in the bone marrow that can be deposited into different tissues or organs. When the protein accumulates in organs such as the heart or kidneys, it can cause damage and even organ failure. One type of amyloidosis is called light chain amyloidosis and involves the overproduction of certain plasma cell proteins, it’s commonly associated with multiple myeloma. Symptoms of amyloidosis may include heart problems; an enlarged liver, spleen or tongue; and skin changes around the eyes.
Multiple myeloma is typically discovered by a doctor unintentionally because signs are not usually present in the early stages of the disease. For example, the disease may be discovered by the results of a blood or urine test done during an annual check-up. Some people with multiple myeloma may have signs that are vague or that may seem related to those of other conditions, and if this is the case, doctors may simply monitor the condition until specific signs appear. Signs of the disease vary among people and depend on the number of myeloma cells in the body and in the area they collect. The most common signs relate to bone and calcium problems, low blood counts, infections and kidney damage (see Staging).
Multiple myeloma cells tend to interfere with bone growth, causing the bones to break down quickly without replenishing themselves. This causes bone weakness and can contribute to an increased amount of calcium in the blood, known as hypercalcemia. The overproduction of abnormal plasma cells also crowds out healthy blood-forming cells and may cause anemia (shortage of red blood cells), leukopenia (shortage of normal white blood cells) and thrombocytopenia (low platelets). These can all result in side effects such as fatigue, increased bleeding and bruising, and an inability to properly fight infections.
The crowding of normal cells may also interrupt the normal production of antibodies, which are created by normal plasma cells in response to harmful infections. However, multiple myeloma cells create M proteins, which continue to reproduce and accumulate (see Figure 4). This buildup not only affects the body’s ability to fight infections but can also lead to kidney damage and possibly kidney failure.