Monoclonal gammopathy of undetermined significance pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omer Kamal, M.D.[2]
Overview
Pathologically, the lesion in Monoclonal gammopathy of undetermined significance is in fact very similar to that in multiple myeloma. What causes Monoclonal gammopathy of undetermined significance to transform into multiple myeloma is as yet unknown.
Pathophysiology
- Pathologically, the lesion in MGUS is in fact very similar to that in multiple myeloma.
- There is a predominance of clonal plasma cells in the bone marrow with an abnormal immunophenotype (CD38+ CD56+ CD19−) mixed in with cells of a normal phenotype (CD38+ CD56− CD19+).[1][2]
- In MGUS, more than 3% of the clonal plasma cells have the normal phenotype, whereas in multiple myeloma, less than 3% of the cells have the normal phenotype.[3] What causes MGUS to transform into multiple myeloma is as yet unknown.
- The transformation of normal plasma cells to MGUS to multiple myeloma involves several steps of gene mutations.[4]
- After the stimulation by the antigens due to toll-like cell receptors expression, overexpression of interleukin receptors for example IL-6 and loss of regulation of cyclin D gene.[5][6][7]
- Patients with MGUS may have a "gamma-spike" on serum electrophoresis, as shown below:
References
- ↑ Zhan F, Hardin J, Kordsmeier B, Bumm K, Zheng M, Tian E, Sanderson R, Yang Y, Wilson C, Zangari M, Anaissie E, Morris C, Muwalla F, van Rhee F, Fassas A, Crowley J, Tricot G, Barlogie B, Shaughnessy J (2002). "Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells". Blood. 99 (5): 1745–57. PMID 11861292.
- ↑ Magrangeas F, Nasser V, Avet-Loiseau H, Loriod B, Decaux O, Granjeaud S, Bertucci F, Birnbaum D, Nguyen C, Harousseau J, Bataille R, Houlgatte R, Minvielle S (2003). "Gene expression profiling of multiple myeloma reveals molecular portraits in relation to the pathogenesis of the disease". Blood. 101 (12): 4998–5006. PMID 12623842.
- ↑ Ocqueteau M, Orfao A, Almeida J, Bladé J, González M, García-Sanz R, López-Berges C, Moro M, Hernández J, Escribano L, Caballero D, Rozman M, San Miguel J (1998). "Immunophenotypic characterization of plasma cells from monoclonal gammopathy of undetermined significance patients. Implications for the differential diagnosis between MGUS and multiple myeloma". Am J Pathol. 152 (6): 1655–65. PMID 9626070.
- ↑ Chng WJ, Glebov O, Bergsagel PL, Kuehl WM (December 2007). "Genetic events in the pathogenesis of multiple myeloma". Best Pract Res Clin Haematol. 20 (4): 571–96. doi:10.1016/j.beha.2007.08.004. PMC 2198931. PMID 18070707.
- ↑ Jego G, Bataille R, Geffroy-Luseau A, Descamps G, Pellat-Deceunynck C (June 2006). "Pathogen-associated molecular patterns are growth and survival factors for human myeloma cells through Toll-like receptors". Leukemia. 20 (6): 1130–7. doi:10.1038/sj.leu.2404226. PMID 16628189.
- ↑ Dinarello CA (February 2009). "Targeting the pathogenic role of interleukin 1{beta} in the progression of smoldering/indolent myeloma to active disease". Mayo Clin. Proc. 84 (2): 105–7. doi:10.4065/84.2.105. PMC 2664579. PMID 19181642.
- ↑ Merlini G, Palladini G (2012). "Differential diagnosis of monoclonal gammopathy of undetermined significance". Hematology Am Soc Hematol Educ Program. 2012: 595–603. doi:10.1182/asheducation-2012.1.595. PMID 23233640.