Plasma cell myeloma

Osserman, B. F., and Lawlor, D. P., Immuno electrophoretic characterisation of the serum and urinary proteins in plasma cell myeloma and Waldenstrom macroglobulinaemia. Ann. N.Y. Acad. Set. 94, 93-97 (1961). 

CLL/SLL, Chronic lymphocytic leukemia/small lymphocytic lymphoma MCL, mantle cell lymphoma FL, follicular lymphoma MZL/MALT, marginal zone lymphoma/mucosa-associated lymphoid tisuse lymphoma SMZL, splenic marginal zone lymphoma HCL, hairy cell leukemia DLCL, diffuse large-cell lymphoma PCM, plasma cell myeloma BCL-1, cyclin D1 FDC MW, Follicular dendritic cell meshworks CK, cytokeratin LELs, lymphoepitheilal lesions. 

S., Scheper, R. J., and Dalton, W. S. (1993) P-glycoprotein expression in human plasma cell myeloma correlation with prior chemotherapy. Blood 81, 490M95. 

H2. Handley, D. A., and Arney, G. K., Plasma cell myeloma and associated amino-acid disorder. Arch. Intern. Med. 120, 353-355 (1967). 

Acronycine (57), isolated in the Lilly laboratories from different Acronychia spp. (Rutaceae), has shown the broadest experimental tumour activity of any alkaloid studied. It was first isolated from Acronychia baueri Its activity against C-I498 myelogenous leukaemia, X-5563 plasma cell myeloma, and adenocarcinoma 755 was found by the Lilly group.Acronycine has been obtained by different syntheses however, no evidence for clinical trials with acronycine has yet been found in the literature. 

Ferry JA, Young RH, Scully RE. Testicular and epididymal plasmacytoma a report of 7 cases, including three that were the initial manifestation of plasma cell myeloma. Am ] Surg Pathol. 1997 21 590. 

The two geminal methyl groups at C-3 appear as an important structural requirement for antitumor activity in the series. Indeed, 3-hydroxymethylacronycine (321. obtained by addition of acronycine to a metabolizing culture of Streptomyces spectabilicus, was devoid of antitumor activity when tested in mice implanted with X-5563 plasma cell myeloma or C-1498 myelogenous leukemia (36). More recently, Reisch et al. prepared... 

The experimental systems of special interest which are responsive to this alkaloid are X- 63 plasma cell myeloma, a model system of multiple myeloma in manj Shionogi carcinoma ll5 an androgen-dependent tumor, potentially a model system for prostatic cancer the C-114 98 myelogenous leukemia which is nonresponsive to any of the clinically useful chemotherapeutic agents. 

Proteasomal inhibition represents a novel strategy in cancer treatment and the small molecule Bortezomid (PS-341, Velcade ) has been approved for the treatment of refractory and relapsed multiple myeloma, a proliferative disease of plasma cells. Bortezomid inhibits an active site in a proteasome subunit and remarkably shows selective cytotoxicity to cancer cells. Although the underlying mechanisms are not completely understood bortezomid apparently induces a cell stress response in these tumor cells followed by caspase-dependent apoptosis. Whether bortezomid is beneficial for the treatment of other proliferative disease is currently being tested in clinical trials. 

Myeloma is a plasma cell cancer associated with bone disease that can be improved by bisphosphonates. 

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... 

A myeloma is a cancer of the antibody-producing plasma cell and as such is immortal. 

Hybridoma Cell produced by the fusion of antibody-producing plasma cells with myeloma/carcinoma cells. The resultant hybrids have then the capacity to produce antibody (as determined by the properties of the plasma cells), and can be grown in continuous culture indefinitely owing to the immortality of the myeloma fusion partner. This technique enabled the first continuous supply of monoclonal antibodies to be produced. 

Willems, P.M., Hoet, R.M., Huys, E.L., Raats, J.M., Mensink, E.J., Raymakers, R.A. (1998). Specific detection of myeloma plasma cells using anti-idiotypic single chain antibody fragments selected from a phage display library. Leukemia, 12, 1295-1302. 

Eisen, H.N., Simms, E.S., Potter, M. (1968). Mouse myeloma proteins with antihapten antibody activity. The protein produced by plasma cell tumor MOPC-315. Biochemistry 7, 4126-4134. 

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%). 

D14. Dewald, G. W., Kyle, R. A., Hicks, G. A., and Greipp, P. R., The clinical significance of cytogenetic studies in 100 patients with multiple myeloma, plasma cell leukemia, or amyloidosis. Blood 66, 380-390 (1985). 

H7. Harada, H., Kawano, M. M., Huang, N., Harada, Y., Iwato, K., Tanabe, O., Tanaka, H., Sakai, A., Asaoku, H., and Kuramoto, A., Phenotypic difference of normal plasma cells from mature myeloma cells. Blood 81, 2658—2663 (1993). 

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