Question

PLEASE QUICK. 1. Briefly elaborate on two distinct clinical diagnostic tests used for diagnosis of multiple myeloma. Be sure to explain the cellular/molecular basis for each test.

Answer 1

Multiple Myeloma- Multiple myeloma is a form of blood cancer of the plasma cells within the bone marrow. Plasma cells constitute an important class of lymphocytes (while blood cells) that are matured form of the B-cells and participate in the innate immune response by secreting immunoglobulins or antibodies against specific antigens. In multiple myeloma, the plasma cells no longer secrete healthy antibodies, rather secrete abnormal monoclonal proteins or the M proteins. Multiple myeloma is a clinical condition characterized by the outgrowth of plasma cells within the bone marrow leading to 'multiple' bone lesions in the patient increasing the risk of bone fractures. Hence the name, multiple myeloma. The increased population of plasma cells prevent the growth of other blood cell types in the bone marrow leading to clinical symptoms such as anemia (shortage of RBC), reduced immunity (shortage of other WBCs), prevention of blood-clotting at the areas of cuts and wounds (shortage of platelets). When the M protein increases in the blood stream of multiple myeloma patients, it may cause kidney damage and other organ failure.

Diagnostic tests for multiple myeloma-  

(1) SPEP and UPEP- Serum protein electrophoresis (SPEP) and Urine protein electrophoresis (UPEP) are the most common clinical diagnostic tests to identify multiple myeloma. In these tests, the heavy chain of the circulating M protein is detected in blood and urine by electrophoresis. In this test the blood and urine samples are run in an electrophoresis gel and the proteins are separated based on their charges and masses. As shown in the figure below, in a normal blood sample, the most abundant protein is the albumin shown as a spike. Apart from albumin, three types of globulin proteins- alpha (1 and 2), beta and gamma globulins are also detected in the blood although as smaller spikes. However, in the case of patient blood of multiple myeloma, we observe a huge spike in gamma globulin in addition to albumin.

(2) SFLC assay- Serum free light chain (SFLC) assay is another important diagnostic test for multiple myeloma. Immunoglobulins are made up of heavy and light chains that are linked together to form a functional immunoglobulin. Plasma cells usually secrete slightly excess light chains directly into the blood stream that do not combine with the heavy chains. Again the light chains are of two types- kappa and lambda. In the clinical condition of multiple myeloma, the amount of light chains secreted by the plasma cells increases significantly which is detected in the SFLC assay. The test also detects an abnormal ratio of kappa/lambda chains in the blood serum of the patients but not in the normal blood of the healthy individuals.