Multiple myeloma proteins

Multiple myeloma is a malignancy of plasma cells that is characterized by an abnormal production of a monoclonal protein. Features of the disease include bone lesions, anemia, and... 

P2 Microglobulin A low-molecular-weight protein that may be elevated in multiple myeloma. 

Vande Broek I, Asosingh K, Vanderkerken K, et al. Chemokine receptor CCR2 is expressed by human multiple myeloma cells and mediates migration to bone marrow stromal cell-produced monocyte chemotactic proteins MCP-1, -2, and -3. Br J Cancer 2003 88 855-862. 

Boc-E4 Boc-EAR lR-MCA BJP-B6 + MCA Autoantibodies Bence Jones proteins (BJPs) (monoclonal antibody light chains) isolated from the urine of multiple myeloma patients, were found to hydrolyse peptide methylcoumarin amide peptide-MCA substrates 1.5 x 101 3.3 X 1()-2 nr 5.8... 

Thus, in 1964, Clough and Rcah (C14) observed that over a three-year period 15 new cases of multiple myeloma had been detected in their Biochemistry Department, entirely by careful examination of urine and serum proteins. 

A viral etiology has been implicated in Burkitt s lymphoma, and there is some evidence that Epstein-Barr virus causes infectious mononucleosis in Europe and Burkitt s lymphoma in Africa. It has been suggested that if the cause of the Burkitt s lymphoma is viral, then entry of the virus particles into the lymphoid colls of the body may derange a part of the cell immune process, subsequently affecting the production of the IgM antibody, a theory which is compatible to the dysproteinemia sometimes seen in multiple myeloma and other lymphomas (N2). Also in support of this is the observation that C-reactive protein was markedly elevated in the serum of patients with Burkitt s lymphoma, and disappeared entirely from the blood when they were cured (MIO). The relationship between malarial infection and Burkitt s lymphoma has been dealt with in a previous section on malaria. 

Chen, Q., B. Gong, A.S. Mahmoud-Ahmed, A. Zhou, E.D. Hsi, M. Hussein, and A. Ahnasan, Apo2L/TRAIL and Bcl-2-related proteins regulate type I interferon-induced apoptosis in multiple myeloma. Blood, 2001. 98(7) 2183-92. 

Isophorone produced kidney effects in male rats in the NTP (1986) study. Strasser (1988) found that isophorone caused protein droplet formation in the kidneys of male rats, suggesting that isophorone can induce protein nephropathy. Alden (1986) discussed the possibility that proteinuric humans and humans with low molecular weight protein nephropathy, such as people with multiple myeloma (Bence-Jones protein) or mononuclear cell leukemia (lysozyme), may be more susceptible to chemically-induced protein nephropathy. He concluded, however, that this syndrome is probably specific to the male rat. 

Jazirehi AR, Bonavida B. 2004. Resveratrol modifies the expression of apoptotic regulatory proteins and sensitizes non-Hodgkin s lymphoma and multiple myeloma cell lines to paclitaxel-induced apoptosis. Mol Cancer Ther 3 71-84. 

Vasef, M. A., Medeiros, J., Yospur, L. S., Sun, N. C. J., McCourty, A., and Brynes, R. K. 1997b. Cyclin D1 protein in multiple myeloma and plasmacytoma An immunohistochemical study using fixed, paraffin-embedded tissue sections. Mod Pathol. 10 927-932. 

Bortezomib. Bortezomib (Velcade) inhibits pro-teasome activity in mammalian cells.11 Mammalian proteasome is responsible for degrading certain cellular proteins affecting cell function and division. By prolonging the activity of these proteins, bortezomib brings about complex changes in cell function that lead to cell dysfunction and death. Certain types of cancer, such as multiple myeloma, are more sensitive to impaired proteasome regulation, hence the use of this drug in these cancers. 

This plasma cell malignancy is one of the models of neoplastic disease in humans because it arises from a single tumor stem cell, and the tumor cells produce a marker protein (myeloma immunoglobulin) that allows the total body burden of tumor cells to be quantified. Multiple myeloma principally involves the bone marrow and the surrounding bone, causing bone pain, lytic lesions, bone fractures, and anemia as well as an increased susceptibility to infection. 

In multiple myeloma, the neoplastic plasma cells secrete monoclonal proteins such as either IgG or IgA. Generally, either k or A. light chains are secreted. These M (monoclonal) proteins can be detected by serum and urine protein zone and immunofixation electrophoretic techniques, the latter providing better discrimination. The immunoglobulin levels exceed 25 g/L. Quantitation of immunoglobulins can be performed by rate nephelometry. 

Monoclonal protein can be detected in serum, urine, or both in greater than 95% of patients with multiple myeloma (D16). Bone marrow plasma cells exceed 10%. Patients with advanced disease may excrete Bence-Jones proteins in urine. Both hypercalcemia and Bence-Jones proteinuria can contribute to renal failure (A6). 

Unless M protein concentrations exceed 60 g/L, patients with multiple myeloma do not develop hyperviscosity syndrome. Despite the presence of plasma cells in bone marrow exceeding 10% and the presence of M protein exceeding 25 g/L, nearly 15% of patients with multiple myeloma are asymptomatic. However, asymptomatic patients presenting with IgA myeloma protein and M protein concentrations exceeding 30 g/L and Bence Jones-protein excretion in excess of 50 mg/day in presence of a lytic bone lesion can progress to multiple myeloma earlier than other, asymptomatic patients (Wl). 

The distinction between essential monoclonal gammopathy and asymptomatic multiple myeloma can be difficult in subjects whose M protein and Bence-Jones protein ranges and percentage of plasma cells in bone marrow overlap. 

Patients without coexisting multiple myeloma or WM secrete small amounts of M protein (< 10 g/L) and their bone marrow is infiltrated with a lesser percentage of atypical plasma cells similar to that seen in essential monoclonal gammopathy (<10%). 

Interferons are proteins or glycoproteins that are produced either by animal cells or plant cells in response to stimuli or DNA recombinant technology. These drugs are active against malignant neoplasms and have immunomodulating effects. These are useful in chronic hepatitis B, hepatitis C, hairy cell leukemia, myeloid leukemia, follicular lymphoma, carcinoid tumor, multiple myeloma, renal cell carcinoma, multiple sclerosis, chronic granulomatous diseases, blood disorders, common cold, herpes simplex, inflammatory bowel disease, and leishmaniasis. 

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