Genomes and Genes
Summary: A group of related diseases characterized by an unbalanced or disproportionate proliferation of immunoglobulin-producing cells, usually from a single clone. These cells frequently secrete a structurally homogeneous immunoglobulin (M-component) and/or an abnormal immunoglobulin.
- Vacca A, Ribatti D, Roccaro A, Frigeri A, Dammacco F. Bone marrow angiogenesis in patients with active multiple myeloma. Semin Oncol. 2001;28:543-50 pubmed..Both angiogenesis and MMP-2 secretion can account for intramedullary and extramedullary spreading of plasma cells in patients with active MM. ..
- Rajkumar S, Kyle R, Therneau T, Melton L, Bradwell A, Clark R, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood. 2005;106:812-7 pubmed
- Leung N, Rajkumar S. Renal manifestations of plasma cell disorders. Am J Kidney Dis. 2007;50:155-65 pubmed
- Niermeijer J, Eurelings M, van der Linden M, Lokhorst H, Franssen H, Fischer K, et al. Intermittent cyclophosphamide with prednisone versus placebo for polyneuropathy with IgM monoclonal gammopathy. Neurology. 2007;69:50-9 pubmed..We therefore performed a double-blind, randomized, placebo-controlled study of combined oral cyclophosphamide and prednisone in IgM MGUS polyneuropathy...
- Tucci A, Bonadonna S, Cattaneo C, Ungari M, Giustina A, Guiseppe R. Transformation of a MGUS to overt multiple myeloma: the possible role of a pituitary macroadenoma secreting high levels of insulin-like growth factor 1 (IGF-1). Leuk Lymphoma. 2003;44:543-5 pubmed
- Lachmann H, Booth D, Booth S, Bybee A, Gilbertson J, Gillmore J, et al. Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. N Engl J Med. 2002;346:1786-91 pubmed..A genetic cause should be sought in all patients with amyloidosis that is not the reactive systemic amyloid A type and in whom confirmation of the AL type cannot be obtained. ..
- Saeki Y, Mima T, Ishii T, Ogata A, Kobayashi H, Ohshima S, et al. Enhanced production of osteopontin in multiple myeloma: clinical and pathogenic implications. Br J Haematol. 2003;123:263-70 pubmed..Plasma OPN levels may be a useful biomarker for assessing bone destruction in MM and distinguishing MM from MGUS or smouldering MM. ..
- Rajkumar S, Dispenzieri A, Kyle R. Monoclonal gammopathy of undetermined significance, Waldenström macroglobulinemia, AL amyloidosis, and related plasma cell disorders: diagnosis and treatment. Mayo Clin Proc. 2006;81:693-703 pubmed..Updated diagnostic criteria for these disorders, risk stratification models to determine prognosis, and the current management of these diverse entitles are discussed in this review. ..
- Toor A, Ramdane B, Joseph J, Thomas M, O Hara C, Barlogie B, et al. Cardiac nonamyloidotic immunoglobulin deposition disease. Mod Pathol. 2006;19:233-7 pubmed..Concurrent amyloidosis in other organs sheds a unique perspective into the role of local microenvironment in the pathogenesis of systemic Ig deposition disease and amyloidosis. ..
- Kawai Y, Kinoshita K, Arai H, Kuwata A, Fukuoka Y, Yamaoka M, et al. Reduced intensity allogeneic stem cell transplantation for systemic primary amyloidosis refractory to high-dose melphalan. Eur J Haematol. 2004;72:448-50 pubmed..RIST may be feasible and be capable of achieving complete HR along with recovery from nephrotic syndrome with acceptable toxicity. ..
- Kyle R, Therneau T, Rajkumar S, Offord J, Larson D, Plevak M, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med. 2002;346:564-9 pubmed..The initial concentration of serum monoclonal protein was a significant predictor of progression at 20 years. The risk of progression of MGUS to multiple myeloma or related disorders is about 1 percent per year. ..
- Pérez Persona E, Vidriales M, Mateo G, Garcia Sanz R, Mateos M, de Coca A, et al. New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering multiple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells. Blood. 2007;110:2586-92 pubmed..001). Our results show that multiparameter FC evaluation of BMPC at diagnosis is a valuable tool that could help to individualize the follow-up strategy for MGUS and SMM patients. ..
- Lorenz E, Gertz M, Fervenza F, Dispenzieri A, Lacy M, Hayman S, et al. Long-term outcome of autologous stem cell transplantation in light chain deposition disease. Nephrol Dial Transplant. 2008;23:2052-7 pubmed publisher..In cases where kidney dysfunction persists after ASCT, a haematological response may permit successful kidney transplantation with improved graft viability and decreased risk of recurrence. ..
- Mseddi Hdiji S, Haddouk S, Ben Ayed M, Tahri N, Elloumi M, Baklouti S, et al. [Monoclonal gammapathies in Tunisia: epidemiological, immunochemical and etiological analysis of 288 cases]. Pathol Biol (Paris). 2005;53:19-25 pubmed..6% of the cases whereas the IgM represents 8.7% only of the 288 cases of our set which involves three cases of IgD myeloma and six cases of biclonal gammapathy. ..
- Comenzo R, Zhou P, Fleisher M, Clark B, Teruya Feldstein J. Seeking confidence in the diagnosis of systemic AL (Ig light-chain) amyloidosis: patients can have both monoclonal gammopathies and hereditary amyloid proteins. Blood. 2006;107:3489-91 pubmed..These results justify further study of screening for hereditary variants in patients with apparent AL, and highlight the need for practical techniques for identifying fibrils extracted from tissue. ..
- Kyle R, Rajkumar S. Monoclonal gammopathy of undetermined significance. Clin Lymphoma Myeloma. 2005;6:102-14 pubmed..Epidemiologic and statistical methods must be used to evaluate these associations. ..
- Kyle R, Gertz M, Witzig T, Lust J, Lacy M, Dispenzieri A, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003;78:21-33 pubmed..The median duration of survival was 33 months and did not improve from 1985 through 1998. ..
- Kyle R, Rajkumar S. Monoclonal gammopathies of undetermined significance: a review. Immunol Rev. 2003;194:112-39 pubmed..MGUS may be associated with many different disorders, including lymphoproliferative diseases, leukemia, connective tissue disorders, dermatologic diseases, and neurologic disorders. ..
- Grosbois B, Jego P, de Rosa H, Ruelland A, Lancien G, Gallou G, et al. [Triclonal gammopathy and malignant immunoproliferative syndrome]. Rev Med Interne. 1997;18:470-3 pubmed..The origin of three distinct monoclonal proteins may derive from three unrelated clones or alternatively from a single clone in which an isotype switch has occurred...
- Abadie J, Bankson D. Assessment of serum free light chain assays for plasma cell disorder screening in a Veterans Affairs population. Ann Clin Lab Sci. 2006;36:157-62 pubmed..Using the serum FLC results in conjunction with SPEP results improves the sensitivity and specificity for managing VA patients whose clinical presentation indicates the need to evaluate PCD. ..
- Pozzi C, D Amico M, Fogazzi G, Curioni S, Ferrario F, Pasquali S, et al. Light chain deposition disease with renal involvement: clinical characteristics and prognostic factors. Am J Kidney Dis. 2003;42:1154-63 pubmed..Dialysis is worth performing in uremic LCDD patients. ..
- Karlson E, Tanasijevic M, Hankinson S, Liang M, Colditz G, Speizer F, et al. Monoclonal gammopathy of undetermined significance and exposure to breast implants. Arch Intern Med. 2001;161:864-7 pubmed..We find little evidence to support a substantial increased risk of MGUS in women exposed to breast implants. Larger studies are needed to determine if a more modest relationship exists. ..
- Kelly J. Peripheral neuropathies associated with monoclonal gammopathies of undetermined significance. Rev Neurol Dis. 2008;5:14-22 pubmed..MGUS is the most common of the PCDs associated with neurologic disorders, which are easily approached clinically by classifying them as IgM or non-IgM types. ..
- Fonseca R, Bailey R, Ahmann G, Rajkumar S, Hoyer J, Lust J, et al. Genomic abnormalities in monoclonal gammopathy of undetermined significance. Blood. 2002;100:1417-24 pubmed..Similar translocations are found in both MGUS and MM, including t(4;14)(p16.3;q32) and t(14;16)(q32;q23). Moreover, Delta 13 is common in MGUS and unlikely to play a predominant role in the evolution of MGUS to MM. ..
- Nobile Orazio E. IgM paraproteinaemic neuropathies. Curr Opin Neurol. 2004;17:599-605 pubmed..Rituximab has opened the way to more selective and apparently safer immune therapies for this neuropathy, but its efficacy needs to be confirmed by randomized controlled trials. ..
- Hadden R, Nobile Orazio E, Sommer C, Hahn A, Illa I, Morra E, et al. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of paraproteinaemic demyelinating neuropathies: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve . Eur J Neurol. 2006;13:809-18 pubmed..6) For POEMS syndrome, local irradiation or resection of an isolated plasmacytoma, or melphalan with or without corticosteroids, should be considered, with haemato-oncology advice. ..
- Dhodapkar M, Geller M, Chang D, Shimizu K, Fujii S, Dhodapkar K, et al. A reversible defect in natural killer T cell function characterizes the progression of premalignant to malignant multiple myeloma. J Exp Med. 2003;197:1667-76 pubmed
- Seldin D, Choufani E, Dember L, Wiesman J, Berk J, Falk R, et al. Tolerability and efficacy of thalidomide for the treatment of patients with light chain-associated (AL) amyloidosis. Clin Lymphoma. 2003;3:241-6 pubmed..Thus, while thalidomide has activity in AL amyloidosis, it also has significant toxicity in this patient population. ..
- Tursi A, Modeo M. Monoclonal gammopathy of undetermined significance predisposing to Helicobacter pylori-related gastric mucosa-associated lymphoid tissue lymphoma. J Clin Gastroenterol. 2002;34:147-9 pubmed..We report a patient with MGUS and H. pylori infection in whom we noted the progression of gastritis to acquired gastric MALT and gastric MALT to MALT lymphoma during a 3-year follow-up. ..
- Katzmann J, Abraham R, Dispenzieri A, Lust J, Kyle R. Diagnostic performance of quantitative kappa and lambda free light chain assays in clinical practice. Clin Chem. 2005;51:878-81 pubmed..The performance of the FLC assay in this analysis of clinical laboratory data is consistent with results from published retrospective validation studies. ..
- Ilyas A, Gu Y, Dalakas M, Quarles R, Bhatt S. Induction of experimental ataxic sensory neuronopathy in cats by immunization with purified SGPG. J Neuroimmunol. 2008;193:87-93 pubmed..This study suggests that these anti-MAG/SGPG antibodies play a role in the pathogenesis of this neuropathy. ..
- Brown L, Gridley G, Check D, Landgren O. Risk of multiple myeloma and monoclonal gammopathy of undetermined significance among white and black male United States veterans with prior autoimmune, infectious, inflammatory, and allergic disorders. Blood. 2008;111:3388-94 pubmed publisher..Risks for MGUS were generally of similar magnitude. Our results indicate that various types of immune-mediated conditions might act as triggers for MM/MGUS development. ..
- Kyle R. New strategies for MGUS and smoldering multiple myeloma. Clin Adv Hematol Oncol. 2004;2:507, 509 pubmed
- Zhan F, Hardin J, Kordsmeier B, Bumm K, Zheng M, Tian E, et al. Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells. Blood. 2002;99:1745-57 pubmed..Thus, novel candidate MM disease genes have been identified using gene expression profiling and this profiling has led to the development of a gene-based classification system for MM. ..
- Buxbaum J, Gallo G. Nonamyloidotic monoclonal immunoglobulin deposition disease. Light-chain, heavy-chain, and light- and heavy-chain deposition diseases. Hematol Oncol Clin North Am. 1999;13:1235-48 pubmed..More structural analyses of material extracted from deposits in tissue may resolve this issue...
- Hughes D, Cappellini M, Berger M, van Droogenbroeck J, de Fost M, Janic D, et al. Recommendations for the management of the haematological and onco-haematological aspects of Gaucher disease. Br J Haematol. 2007;138:676-86 pubmed..Future studies should focus on the utility of early treatment to prevent immunoglobulin abnormalities and multiple myeloma. ..
- García Marrero R, Alonso Socas M, Oramas Rodríguez J, Alonso Alvarez B, Batista Lopez N. [Several episodes of bacterial infections in a patient with monoclonal gammapathy of undetermined significance]. An Med Interna. 2006;23:452 pubmed
- Comi G, Roveri L, Swan A, Willison H, Bojar M, Illa I, et al. A randomised controlled trial of intravenous immunoglobulin in IgM paraprotein associated demyelinating neuropathy. J Neurol. 2002;249:1370-7 pubmed..Two serious adverse events occurred during the trial, both during placebo treatment. In conclusion the trial showed some short-term benefit of IVIg in about half of the patients confirming previous observation. ..
- Fujita K, Curtiss L, Sakurabayashi I, Kameko F, Okumura N, Terasawa F, et al. Identification and properties of glycated monoclonal IgA that affect the fructosamine assay. Clin Chem. 2003;49:805-8 pubmed
- Asatiani E, Cohen P, Ozdemirli M, Kessler C, Mavromatis B, Cheson B. Monoclonal gammopathy in extranodal marginal zone lymphoma (ENMZL) correlates with advanced disease and bone marrow involvement. Am J Hematol. 2004;77:144-6 pubmed..0007). Prevalence of monoclonal gammopathy is higher than previously recognized and indicates advanced disease. However, the prognostic significance of the presence of monoclonal gammopathy in this population is unknown. ..
- Dhodapkar M, Krasovsky J, Osman K, Geller M. Vigorous premalignancy-specific effector T cell response in the bone marrow of patients with monoclonal gammopathy. J Exp Med. 2003;198:1753-7 pubmed
- Standal T, Hjorth Hansen H, Rasmussen T, Dahl I, Lenhoff S, Brenne A, et al. Osteopontin is an adhesive factor for myeloma cells and is found in increased levels in plasma from patients with multiple myeloma. Haematologica. 2004;89:174-82 pubmed..The elevated plasma OPN levels in myeloma patients could be due to both production of OPN by the tumor cells and tumor-induced production of OPN by non-tumor cells. ..
- Kyle R, Therneau T, Rajkumar S, Larson D, Plevak M, Offord J, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med. 2006;354:1362-9 pubmed..5 percent of 79 tested had a monoclonal urinary light chain. Among residents of Olmsted County, Minnesota, MGUS was found in 3.2 percent of persons 50 years of age or older and 5.3 percent of persons 70 years of age or older. ..
- Kaloterakis A, Cholongitas E, Pantelis E, Papadimitriou C, Durakis S, Filiotou A. Type I Gaucher disease with severe skeletal destruction, extraosseous extension, and monoclonal gammopathy. Am J Hematol. 2004;77:377-80 pubmed..Thus, malignant diseases were excluded and the diagnosis of an extraosseous Gaucher-cell extension was well documented. Our case is reported because it is very interesting and unique in the literature. ..
- Yu R, Ariga T. The role of glycosphingolipids in neurological disorders. Mechanisms of immune action. Ann N Y Acad Sci. 1998;845:285-306 pubmed..This latter observation suggests that SGGLs may also participate in cell-mediated responses in certain inflammatory neurological disorders. ..
- Shiina M, Kusunoki S, Miyazaki T, Kanazawa I. Variability in immunohistochemistries of IgM M-proteins binding to sulfated glucuronyl paragloboside. J Neuroimmunol. 2001;116:206-12 pubmed..Only three patients (all in group B) showed some response to the immunotherapies. Weak reactivities to P0 and and PMP-22 might indicate the possibility of improvement after the immunotherapies. ..
- Sánchez Quintana A, Rull P, Atienza J, McDonnell C. Renal transplant in plasma cell dyscrasias with lenalidomide treatment after autologous stem cell transplantation. Nephrology (Carlton). 2013;18:641-3 pubmed publisher..We also report their perioperative management and their outcome. ..
- Sethi S, Fervenza F, Rajkumar S. Spectrum of manifestations of monoclonal gammopathy-associated renal lesions. Curr Opin Nephrol Hypertens. 2016;25:127-37 pubmed publisher..The term monoclonal gammopathy of renal significance helps highlight patients who have renal disease secondary to monoclonal immunoglobulin secreted by a premalignant or malignant clone, but is not a disease or diagnosis in itself. ..
- Kovarova L, Michalek J, Kyr M, Penka M, Hajek R. [Comparison of dendritic cells antigens in healthy volunteers and monoclonal gammopathy of undetermined significance and/or multiple myeloma patients]. Klin Onkol. 2008;21:20-5 pubmed..Autologous patient serum had negative influence on DCs, with no definite dependance on the IL-6 level. ..
- Magro C, Wang X. CCL5 expression in panniculitic T-cell dyscrasias and its potential role in adipocyte tropism. Am J Dermatopathol. 2013;35:332-7 pubmed publisher..Given the known pharmacologic inhibitors of CCR5-expression one might propose that using such inhibitors (ie, anti-CCR5) could be of therapeutic value in select cases. ..
- Roth R, Benson D, Hebert L, Bissell M, Satoskar A, Nadasdy T, et al. Progressive renal light chain amyloidosis with the absence of detectable free monoclonal light chains after an autologous hematopoietic stem cell transplant for amyloid light chain amyloidosis. Arch Pathol Lab Med. 2013;137:1304-8 pubmed publisher..Unexplained, worsening renal function warrants a kidney biopsy to assess whether retreatment of the monoclonal gammopathy is indicated. ..