Multiple Myeloma or simply myeloma (in Greek Myelos means bone marrow), is known as one of the most devastating cancers affecting humans. Every year around 15,000 people are diagnosed with multiple myeloma in the United States. Survival for a period of 5 years is seen in only 50% people. Genetic transformation of plasma cells (a type of white blood cells concerned with immunity), is the core process responsible for this cancer. Though it solely affects plasma cells, the resulting disease causes widespread changes in nearly all parts of the body.The most commonly involved tissues are bones, blood, and kidney. However, later in the advanced stages there is failure of all organ systems. Complications, like recurrent infections and anemia, considerably reduce the life span and cause early death despite treatment. Generally, it is a disease of the elderly, occurring at an age of above 60 years. However, unfortunately this trend is changing rapidly with newly diagnosed younger patients being on the rise.
In order to understand multiple myeloma it is necessary to understand about
- Bone Marrow – Structure and Function
- Immune System – Structure and Function
Pathogenesis of Multiple Myeloma
Plasma cells are activated B lymphocytes. Normally, antigens present on the surface of infecting organisms or tumor cells cause activation of B lymphocytes to form plasma cells. However, in multiple myeloma, plasma cells are formed from B lymphocytes because of a genetic defect, without any antigenic stimulus. Also, the mechanism regulating the production of antibodies by plasma cells is lost, leading to a continuous production of large quantities random antibodies. This causes depletion of primary proteins, which are raw materials for synthesis of different proteins in the body. It also causes accumulation of large quantities of non-specific antibodies in the kidney for excretion. This puts a tremendous strain on the kidneys as well as causes direct injury to the cells of the kidney. The kidneys reaches a stage where they cannot perform their function of excretion effectively, a condition called as renal failure.
The accumulation of plasma cells in bone marrow causes inadequate production of other blood cells. This causes a plethora of symptoms because of bone marrow failure and consequent cytopenia (cyto = cell & penia = deficiency). The plasma cells also secrete RANKL, which is a chemical substance which stimulates osteoclasts. Osteoclasts are cells which digest bone tissue and release calcium in blood circulation. Excessive activity of osteoclasts leads to erosion of bones and gives rise to the “punched out” defects in bones, which are commonly seen on X-ray examination.
Cause of Multiple Myeloma
Multiple myeloma is a disease of the elderly. The process of aging leads to degenerative changes in several parts of the body. Rapidly dividing cells, like that of bone marrow, have to constantly replicate their DNA (genetic material), which is a complex process. Mistakes in this complex process (mutations) tend to occur and are propagated over generations of cells. A buildup of these mistakes leads to wonderful phenomenon like evolution as well as disasters like chromosomal anomalies. These chromosomal anomalies can lead to production of abnormal cells. Generally, these abnormal cells perish automatically by a process called apoptosis (automatic cell death). However, if the genes controlling apoptosis are lost during chromosomal anomalies, then the cells simply accumulate.
This is the general mechanism how genetic transformation of plasma cells leads to development of multiple myeloma in mostly elderly individuals. The abnormal plasma cells overflow from the bone marrow of origin and via blood are transported to bone marrow in other parts of the body. Thus, bone marrow of the entire body is affected at multiple sites. Hence the name, multiple myeloma – a cancer of bone marrow affecting multiple sites !