Multiple Myeloma

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Multiple myeloma
Multiple myeloma (also plasma cell myeloma also known as MM, myeloma, plasma cell myeloma, or as Kahler's disease) is a progressive hematologic (blood) disease. It is a cancer of the plasma cell, an important part of the immune system that produces immunoglobulins (antibodies) to help fight infection and disease.

The immune system is made up of several types of cells that work together to fight infections. Lymph cells (called lymphocytes) are the main type of cell in the adaptive immune system. There are 2 types of lymph cells: T cells and B cells. When B cells respond to an infection, they change into plasma cells. The plasma cells are found mainly in the bone marrow—the soft, inner part of some bones. The plasma cells make proteins called antibodies that attack and help kill germs. When plasma cells grow out of control, they can form a tumor, usually in the bone marrow. This type of tumor is called a myeloma, and if there are many tumors they are called multiple myeloma. If there is only one tumor, it is called solitary plasmacytoma. In many cases, this single tumor will go on to become multiple myeloma. Multiple myeloma is characterized by excessive numbers of abnormal plasma cells in the bone marrow and overproduction of intact monoclonal immunoglobulin (IgG, IgA, IgD, or IgE) or Bence-Jones protein (free monoclonal light chains). 1 Mechanism of developing malignant plasma cells:

Normally, plasma cells make up a very small portion (less than 5%) of cells in the bone marrow. However, mostly multiple myeloma cell pathogenesis is based on bone marrow microenvironment. The subsets of bone marrow cell components including stromal cells, osteoclasts, and osteoblasts can modify growth advantage, survival and drug resistance of MM cells. Myeloma plasma cells, however, have specific adhesion molecules on their surface allowing them to target the bone marrow where they attach to structural cells called stromal cells. 2Once myeloma cells attach to bone marrow stromal cells, several interactions cause myeloma cells to grow: Both myeloma cells and stromal cells produce chemical messengers called cytokines. These cytokines stimulate the growth of myeloma cells and inhibit (prevent) natural cell death (called apoptosis), leading to proliferation of myeloma cells and ultimately resulting in bone destruction. Myeloma cells also produce growth factors that promote angiogenesis, the creation of new blood vessels. These new blood vessels provide the oxygen and nutrients that promote tumor growth. A growth factor called vascular endothelial growth factor (VEGF) plays a key role in angiogenesis. Angiogenesis encourages reproduction of myeloma cells, which increase in number and begin to infiltrate the bone marrow, eventually comprising more than 10% of the cells present. Mature myeloma cells may fail to activate the immune system and may produce substances that decrease the body's normal immune response to a foreign body. Thus, the cells can grow unchecked. 3

As tumors grow, they invade the hard outer part of the bone, the solid tissue. In most cases, the myeloma cells spread into the cavities of all the large bones of the body, forming multiple small lesions. This is why the disease is known as "multiple" myeloma. In some cases, collections of plasma cells arise either within bone or in soft tissues as masses or tumors. These collections are called plasmacytomas, and may represent a more aggressive form of myeloma.

Myeloma cells are identical and produce the same immunoglobulin protein, called monoclonal (M) protein or paraprotein, in large quantities. Although the specific M protein varies vary from patient to patient, it is always exactly the same in any one patient. When blood or urine is processed in a laboratory test called electrophoresis, these M proteins show up as a "spike" in the results.

Unlike normal immunoglobulin, M protein does not benefit the body. Instead, it crowds out normal, functional...
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