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Multiple myeloma is a monoclonal malignancy of plasma cells in the bone marrow resulting in their overproduction and production of large quantities of functionless immunoglobulins.
It is the second most common cancer affecting older people. The cause of this kind of disease is still not known.
The neoplastic event in myeloma may involve cells earlier in B-cell differentiation than the plasma cell. Interleukin (IL) 6 may play a role in driving myeloma cell proliferation.
The most common presenting features of multiple myeloma are:
CRAB mnemonic stands for C-High calcium levels, R-Renal problems, A-Anemia and B- Bone problems
In a typical individual vertebra is a site for hematopoiesis of the hematopoietic stem cells. Normal bone marrow has less than 5% plasma cells that secrete antibodies to protect the body.
The antibodies that are secreted by the plasma cells have a normal heavy and light chain.
In multiple myeloma, the hematopoietic stem cells shift production to mainly produce more B cells and plasma cells ending up with more than 10 % of plasma cells producing abnormal antibodies.
In about 75% of the cases, these abnormal antibodies produced have only light chains. These light chains are known as power proteins.
The main antibodies found associated with multiple myeloma are immunoglobulin A and immunoglobulin G.
Normal bone has three main types of cells.
Osteoblasts in the presence of calcium and phosphates produce strong bones. Osteoclasts, on the other hand, break down bones by secreting hydrochloric acid. This results in the release of calcium and phosphorus into the blood. Osteoblasts and osteoclasts regulate each other.
Osteoclasts activation is regulated by osteoblasts that express RANKL (Ligand). (Receptor activator of nuclear factor κ B )The RANKL binds to RANK on the osteoblasts receptors stimulating osteoblast activity but osteoblasts secrete another molecule called osteoprotegerin (OPG) which inhibits the interaction, therefore, reducing osteoclast activity.
Osteoclastic activity is triggered via the osteoblasts' surface-bound RANKL activating the osteoclasts' surface-bound receptor activator of nuclear factor kappa-B (RANK).
RANKL is an apoptosis regulator gene, a binding partner of osteoprotegerin (OPG)
In multiple myeloma, the bone marrow stromal cells interact with these cancerous cells through receptors and cytokines. Adhesion of the multiple myeloma cells to the bone marrow stromal cells results in cytokine-mediated growth, survival, resistance, and migration. This means that the bone marrow stromal cells promote the growth and development of multiple myeloma cells.
These effects are due both to direct MM cell–BMSC binding and to induction of various cytokines, including IL-6, insulin-like growth factor type I (IGF-I), vascular endothelial growth factor (VEGF), and stromal cell-derived growth factor (SDF)-1α.
Multiple myeloma cells have the ability to release cytokines that can have effects on the body such as interleukin 6 which reduces osteoblast activity by inhibiting osteoblast progenitor cells to become osteoblasts, therefore, leading to reduced osteoblast numbers.
These malignant cells also release Dickhoff-1 DKK-1 which inhibits OPG produced by the osteoblast resulting in an increased osteoclast population. Multiple myeloma cells also stimulate osteoclast activity by producing the MIP alpha component and Rank L.
The osteoclasts can self-stimulate through bone marrow stromal cells and IL6. This image then results in the amplification of multiple myeloma cells in the bone marrow increasing osteoclast activity and reducing osteoclast activity in the bones.
With the amplified osteoclastic activity then there is an increased breakdown of the bones leading to an increased susceptibility to fractures and the development of bone lytic lesions and hypercalcemia.
In the blood, there is also paraproteins production with bits of light chains floating around. These types of proteins have also a negative effect on the body. They are produced by multiple myeloma cells.
These light chain types of proteins known as power proteins are small enough to get filtered through the glomerulus eventually causing kidney failure in about 20 - 30 % of the cases.
The light chains are then passed into the urine. This is one of the classical features of multiple myeloma known as Bence Jones proteins
Multiple myelomas also lead to anemia in various ways as follows:
For a detailed discussion of the diagnosis and differential diagnosis of multiple myeloma you can get the theme in our previous article here:
Blood tests when performed on these patients can show;
Patients with myeloma also have a decreased anion gap [i.e., Na+ – (Cl− + HCO3−)] because the M component is cationic, resulting in the retention of chloride.
Bone marrow biopsy indicates more than 10% of plasma cells (Confirmatory).
Bone marrow aspiration
X-Rays indicate osteoporosis or diffuse osteopenia.
CT scan shows punched-out lytic lesions. (Mostly in the vertebrae, ribs, pelvic bones, and bones of the thigh and upper arm)