Introduction to myeloma pathogenesis

Myeloma is a blood cancer arising from plasma cells, a type of white blood cell, that are normally found in the bone marrow. Malignant plasma cells, also known as myeloma cells, mostly accumulate in the bone marrow and only rarely enter the bloodstream in significant quantities.

As a consequence, the major effects and complications of myeloma occur in the bone marrow, resulting in:

• Disruption of normal bone marrow function, including the production of healthy red cells, most commonly reflected by anaemia
• Bone damage, known as myeloma bone disease, to affected bones causing lytic bone lesions and fractures
• Suppression of immune function, reflected by reduced levels of normal immunoglobulins and increased susceptibility to infection

Myeloma cells produce an abnormal monoclonal immunoglobulin protein (called paraprotein or M protein) which has further direct consequences, including:

• Blocking of renal tubules, resulting in renal damage
• Hyperviscosity syndrome, due to high levels of paraprotein in the serum

Renal damage also occurs as a consequence of the production of excessive amounts free light chain (also called Bence-Jones protein), a component of the immunoglobulin molecule, by the myeloma cell. Bence-Jones proteins are small enough to pass across the renal glomerulus into the urine. They are intrinsically toxic to the kidney and in high concentrations, such as those seen in myeloma, can damage the renal tubules.

In some patients, myeloma cells do not produce whole immunoglobulin molecules but only free light chains. This is known as light chain or Bence-Jones myeloma and accounts for about 20% of myeloma cases.

Myeloma cells adhere to the stromal (or support) cells of the bone marrow and trigger the secretion of chemical messengers, known as cytokines. This leads to the activation of many different cellular pathways that help support the growth of the myeloma cells and at the same time, the destruction of bone. The latter is a consequence of the increased activation of osteoclasts, the cells responsible for the breakdown of bone in the normal bone remodelling process, and impaired function of osteoblasts, cells which create new bone. This is referred to as myeloma bone disease and is covered in more detail in Module 8.

Research into the pathogenesis of myeloma has identified several pathways that are activated and therefore potential targets for new myeloma treatments. These include the cell signalling pathways NF-κB, IL6, RAS and FGFR3. The RANK-RANKL-OPG pathway has been shown to be important in osteoclast activation and is being targeted for the treatment of myeloma bone disease. This is described in greater detail in Module 9. An appreciation of the pathogenesis of myeloma is important. Understanding how myeloma presents, how it can be treated and how targeted drug treatment can improve patients’ outcomes, can determine how nurses respond to patient needs.