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Monoclonal gammopathy of undetermined significance

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https://www.readbyqxmd.com/read/29669929/antigen-mediated-regulation-in-monoclonal-gammopathies-and-myeloma
#1
Shiny Nair, Joel Sng, Chandra Sekhar Boddupalli, Anja Seckinger, Marta Chesi, Mariateresa Fulciniti, Lin Zhang, Navin Rauniyar, Michael Lopez, Natalia Neparidze, Terri Parker, Nikhil C Munshi, Rachael Sexton, Bart Barlogie, Robert Orlowski, Leif Bergsagel, Dirk Hose, Richard A Flavell, Pramod K Mistry, Eric Meffre, Madhav V Dhodapkar
A role for antigen-driven stimulation has been proposed in the pathogenesis of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) based largely on the binding properties of monoclonal Ig. However, insights into antigen binding to clonal B cell receptors and in vivo responsiveness of the malignant clone to antigen-mediated stimulation are needed to understand the role of antigenic stimulation in tumor growth. Lysolipid-reactive clonal Ig were detected in Gaucher disease (GD) and some sporadic gammopathies...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29656787/fifty-year-incidence-of-waldenstr%C3%A3-m-macroglobulinemia-in-olmsted-county-minnesota-from-1961-through-2010-a-population-based-study-with-complete-case-capture-and-hematopathologic-review
#2
Robert A Kyle, Dirk R Larson, Ellen D McPhail, Terry M Therneau, Angela Dispenzieri, Shaji Kumar, Prashant Kapoor, James R Cerhan, S Vincent Rajkumar
OBJECTIVE: To determine the incidence of Waldenström macroglobulinemia (WM) in a strictly defined geographic area over a 50-year period. PATIENTS AND METHODS: All residents of Olmsted County with a diagnosis of WM, consisting of a monoclonal IgM protein of any size and/or 10% or more lymphoplasmacytic infiltration of the bone marrow along with anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly requiring therapy, were identified from January 1, 1961, to December 31, 2010...
April 12, 2018: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/29651353/a-rare-case-of-systemic-al-amyloidosis-with-muscle-involvement-a-misleading-diagnosis
#3
Fabrizio Accardi, Valentina Papa, Anna Rita Capozzi, Gian Luca Capello, Laura Verga, Cristina Mancini, Eugenia Martella, Roberta Costa, Laura Notarfranchi, Benedetta Dalla Palma, Franco Aversa, Vladimiro Pietrini, Giovanna Cenacchi, Nicola Giuliani
Muscle involvement in AL amyloidosis is a rare condition, and the diagnosis of amyloid myopathy is often delayed and underdiagnosed. Amyloid myopathy may be the initial manifestation and may precede the diagnosis of systemic AL amyloidosis. Here, we report the case of a 73-year-old man who was referred to our center for a monoclonal gammopathy of undetermined significance (MGUS) diagnosed since 1999. He reported a progressive weakness of proximal muscles of the legs with onset six months previously. Muscle biopsy showed mild histopathology featuring alterations of nonspecific type with a mixed myopathic and neurogenic involvement, and the diagnostic turning point was the demonstration of characteristic green birefringence under cross-polarized light following Congo red staining of perimysial vessels...
2018: Case Reports in Hematology
https://www.readbyqxmd.com/read/29629484/light-chain-monoclonal-gammopathy-of-undetermined-significance-is-characterized-by-a-high-disappearance-rate-and-low-risk-of-progression-on-longitudinal-analysis
#4
Benedikt W Pelzer, Marina Arendt, Susanne Moebus, Lewin Eisele, Karl-Heinz Jöckel, Ulrich Dührsen, Jan Dürig
We determined the 10-year progression rate of light chain monoclonal gammopathy of undetermined significance (LCMGUS) and investigated potential associations with cancer utilizing the German population-based Heinz Nixdorf Recall Study. The Heinz Nixdorf Recall Study comprises 4814 men and women aged 45-75 years. Serum samples from baseline (2000-2003) and five-year (2006-2008) and 10-year (2011-2015) follow-up examinations were screened for monoclonal free light chains (FLC). LCMGUS was defined as abnormal FLC ratio, increase of involved FLC with complete loss of immunoglobulin heavy chain, and absence of a history of lymphoproliferative disease (LPD)...
April 9, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29616856/oncogene-induced-senescence-a-potential-breakpoint-mechanism-against-malignant-transformation-in-plasma-cell-disorders
#5
Nicola Lehners, Elena Ellert, Jing Xu, Jens Hillengass, Jonas Leichsenring, Albrecht Stenzinger, Hartmut Goldschmidt, Mindaugas Andrulis, Marc S Raab
Oncogene-induced senescence (OIS) is a cellular tumor-suppressive mechanism present in several premalignant conditions. Here, we analyze the possible impact of OIS on malignant transformation in plasma cell disorders. Tumor samples from 125 patients with different disease stages were analyzed immunohistochemically for expression of senescence markers. Protein expression of cyclin-dependent kinase inhibitor p21Cip1/Waf1 was significantly higher in smoldering multiple myeloma (SMM) compared to monoclonal gammopathy of undetermined significance (MGUS) (p = ...
April 4, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29589107/rhu-epo-down-regulates-pro-tumorigenic-activity-of-cancer-associated-fibroblasts-in-multiple-myeloma
#6
Vanessa Desantis, Maria Antonia Frassanito, Roberto Tamma, Ilaria Saltarella, Lucia Di Marzo, Aurelia Lamanuzzi, Antonio Giovanni Solimando, Simona Ruggieri, Tiziana Annese, Beatrice Nico, Angelo Vacca, Domenico Ribatti
We have previously demonstrated that recombinant human erythropoietin (rHuEpo) is involved in the regulation of the angiogenic response in multiple myeloma (MM) through a direct effect on macrophages and endothelial cells isolated from the bone marrow of patients with MM. The aim of the present study was designed to determine the effects of rHuEpo on cancer-associated fibroblasts (CAFs) from monoclonal gammopathy of undetermined significance (MGUS) and MM patients by means of in vitro and in vivo assays. rHuEpo treatment reduces the expression of mRNA levels of fibroblast activation markers, namely alpha smooth actin (αSMA) and fibroblast activation protein (FAP) in MGUS and MM CAFs, and of pro-inflammatory and pro-angiogenic cytokines, including interleukin (IL)-6 and IL-8, vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor-2 (FGF-2), and hepatocyte growth factor (HGF) in MM CAFs...
March 28, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29578430/development-of-ganglionopathy-and-tabetic-visceral-crises-on-the-background-of-polyradiculoneuropathy-associated-with-monoclonal-gammopathy-case-report
#7
R Svistilnik, N Kostiukova
The article presents an analysis of the clinical occurrence of development of chronic polyradiculoneuropathy associated with monoclonal IgG/k (kappa) gammopathy of the undetermined significance. The peculiarity of this occurrence is the uniqueness of the development of the symptoms which are characteristic of tabes dorsalis in this pathology with episodic severe visceral crises and also with ganglionopathy. The example describes the clinical polymorphism of the course of visceral crises, the problems of their diagnosis and as a consequence of inadequate treatment with the development of severe social maladaptation...
February 2018: Georgian Medical News
https://www.readbyqxmd.com/read/29571269/a-functional-assay-to-identify-amyloidogenic-light-chains
#8
Emily B Martin, Angela D Williams, R Eric Heidel, James S Foster, Ronald H Lands, Stephen J Kennel, Jonathan S Wall
INTRODUCTION: Multiple myeloma (MM) and light chain monoclonal gammopathy of undetermined significance (LCMGUS) are plasma cell disorders associated with the secretion of monoclonal free light-chain (LC) proteins. Due to the high concentrations of LC in circulation, both of these populations are at risk for developing LC-associated amyloidosis (AL) - a protein misfolding disease characterized by the deposition of LC protein fibrils in organs and tissues, leading to dysfunction and significant morbidity...
March 23, 2018: Amyloid: the International Journal of Experimental and Clinical Investigation
https://www.readbyqxmd.com/read/29568092/prognostic-significance-of-interphase-fish-in-monoclonal-gammopathy-of-undetermined-significance
#9
Arjun Lakshman, Shilpa Paul, S Vincent Rajkumar, Rhett P Ketterling, Patricia T Greipp, Angela Dispenzieri, Morie A Gertz, Francis K Buadi, Martha Q Lacy, David Dingli, Amie L Fonder, Suzanne R Hayman, Miriam A Hobbs, Wilson I Gonsalves, Yi Lisa Hwa, Prashant Kapoor, Nelson Leung, Ronald S Go, Yi Lin, Taxiarchis V Kourelis, Rahma Warsame, John A Lust, Stephen J Russell, Steven R Zeldenrust, Robert A Kyle, Shaji K Kumar
No abstract text is available yet for this article.
January 30, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29567768/highly-sensitive-myd88-l265p-mutation-detection-by-droplet-digital-pcr-in-waldenstr%C3%A3-m-macroglobulinemia
#10
Daniela Drandi, Elisa Genuardi, Irene Dogliotti, Martina Ferrante, Cristina Jiménez, Francesca Guerrini, Mariella Lo Schirico, Barbara Mantoan, Vittorio Muccio, Giuseppe Lia, Gian Maria Zaccaria, Paola Omedè, Roberto Passera, Lorella Orsucci, Giulia Benevolo, Federica Cavallo, Sara Galimberti, Ramón García-Sanz, Mario Boccadoro, Marco Ladetto, Simone Ferrero
We here describe a novel method for MYD88L265P mutation detection and minimal residual disease monitoring in Waldenström Macroglobulinemia, by droplet digital PCR, in bone marrow and peripheral blood cells, as well as in circulating cell free DNA. Our method shows a sensitivity of 5.00E-05, by far superior to the widely used allele-specific polymerase chain reaction (1.00E-03). Overall, 291 unsorted samples from 148 patients (133 Waldenstrom 11 IgG-lymphoplasmacytic lymphoma and 4 IgM-monoclonal gammopathy of undetermined significance), 194 baseline and 97 follow-up, were analyzed...
March 22, 2018: Haematologica
https://www.readbyqxmd.com/read/29531171/loss-of-the-immune-checkpoint-cd85j-lilrb1-on-malignant-plasma-cells-contributes-to-immune-escape-in-multiple-myeloma
#11
Ester Lozano, Tania Díaz, Mari-Pau Mena, Guillermo Suñe, Xavier Calvo, Marcos Calderón, Lorena Pérez-Amill, Vanina Rodríguez, Patricia Pérez-Galán, Gaël Roué, M Teresa Cibeira, Laura Rosiñol, Ignacio Isola, Luis-Gerardo Rodríguez-Lobato, Beatriz Martin-Antonio, Joan Bladé, Carlos Fernández de Larrea
Mechanisms of immune regulation may control proliferation of aberrant plasma cells (PCs) in patients with monoclonal gammopathy of undetermined significance (MGUS) preventing progression to active multiple myeloma (MM). We hypothesized that CD85j ( LILRB1 ), an inhibitory immune checkpoint for B cell function, may play a role in MM pathogenesis. In this study, we report that patients with active MM had significantly lower levels of CD85j and its ligand S100A9. Decreased CD85j expression could also be detected in the premalignant condition MGUS, suggesting that loss of CD85j may be an early event promoting tumor immune escape...
March 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29515067/-sporadic-late-onset-nemaline-myopathy-with-monoclonal-gammopathy-of-undetermined-significance-mimicking-poems-syndrome
#12
Takashi Kanamori, Shigeru Kusumoto, Kenji Okita, Shinya Hagiwara, Chie Kato, Takahiro Nakashima, Satsuki Murakami, Tomoko Narita, Asahi Ito, Masaki Ri, Takashi Ishida, Hirokazu Komatsu, Noriyuki Matsukawa, Shinsuke Iida
A 40-year-old female presented with a skin rash, hepatosplenomegaly, hypothyroidism, IgG-λ monoclonal gammopathy, slightly elevated serum VEGF levels, and >1-year history of weakness in the posterior cervical muscles. Based on these symptoms and her clinical course, she was suspected of having POEMS syndrome. However, because there was no sign of peripheral neuropathy (PN), the criteria for the diagnosis of POEMS syndrome were not met. Consequently, she continued follow-up and was under close observation as an outpatient...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29506935/prognostic-biomarkers-in-the-progression-from-mgus-to-multiple-myeloma-a-systematic-review
#13
REVIEW
Charlotte Cosemans, Bénedith Oben, Ingrid Arijs, Annick Daniëls, Jeroen Declercq, Kimberly Vanhees, Guy Froyen, Brigitte Maes, Jeroen Mebis, Jean-Luc Rummens
Multiple myeloma (MM), characterized by malignant plasma cells in the bone marrow, is consistently preceded by asymptomatic premalignant stage monoclonal gammopathy of undetermined significance (MGUS). These MGUS patients have an annual risk of 1% to progress to MM. Clinical, imaging, and genomic (genetic and epigenetic) factors were identified, whose presence increased the risk of progression from MGUS to MM. In this systematic review we summarize the currently identified clinical, imaging, and genomic biomarkers suggested to increase the progression risk or shown to be differentially expressed/present between both cohorts of patients...
February 17, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29492600/lymphoma-like-monoclonal-b-cell-lymphocytosis-in-a-patient-population-biology-natural-evolution-and-differences-from-cll-like-clones
#14
Sam Vander Meeren, Bert Heyrman, Wim Renmans, Marleen Bakkus, Brigitte Maes, Hendrik De Raeve, Rik Schots, Kristin Jochmans
High-count monoclonal B cell lymphocytosis (MBL) with a chronic lymphocytic leukemia (CLL) phenotype is a well-known entity, featuring 1-4% annual risk of progression towards CLL requiring treatment. Lymphoma-like MBL (L-MBL), on the other hand, remains poorly defined and data regarding outcome are lacking. We retrospectively evaluated 33 L-MBL cases within our hospital population and compared them to 95 subjects with CLL-like MBL (C-MBL). Diagnoses of L-MBL were based on asymptomatic B cell clones with Matutes score < 3, B cells < 5...
February 28, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29450453/the-association-of-age-with-clinical-presentation-and-comorbidities-of-pyoderma-gangrenosum
#15
Hovik J Ashchyan, Daniel C Butler, Caroline A Nelson, Megan H Noe, William G Tsiaras, Stephen J Lockwood, William D James, Robert G Micheletti, Misha Rosenbach, Arash Mostaghimi
Importance: Pyoderma gangrenosum is an inflammatory neutrophilic dermatosis. Current knowledge of this rare disease is limited owing to a lack of validated diagnostic criteria and large population studies. Objective: To evaluate the association of age with the clinical presentation and comorbidities of pyoderma gangrenosum. Design, Setting, and Participants: This was a multicenter retrospective cohort study performed at tertiary academic referral centers in urban settings...
February 14, 2018: JAMA Dermatology
https://www.readbyqxmd.com/read/29448055/proteomic-characterization-of-withaferin-a-targeted-protein-networks-for-the-treatment-of-monoclonal-myeloma-gammopathies
#16
Martin Dom, Fritz Offner, Wim Vanden Berghe, Xaveer Van Ostade
Withaferin A (WA), a natural steroid lactone from the plant Withania somnifera, is often studied because of its antitumor properties. Although many in vitro and in vivo studies have been performed, the identification of Withaferin A protein targets and its mechanism of antitumor action remain incomplete. We used quantitative chemoproteomics and differential protein expression analysis to characterize the WA antitumor effects on a multiple myeloma cell model. Identified relevant targets were further validated by Ingenuity Pathway Analysis and Western blot and indicate that WA targets protein networks that are specific for monoclonal gammopathy of undetermined significance (MGUS) and other closely related disorders, such as multiple myeloma (MM) and Waldenström macroglobulinemia (WM)...
February 12, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29424556/monoclonal-gammopathy-of-undetermined-significance-in-systemic-transthyretin-amyloidosis-attr
#17
Pooja Phull, Vaishali Sanchorawala, Lawreen H Connors, Gheorghe Doros, Frederick L Ruberg, John L Berk, Shayna Sarosiek
OBJECTIVE: To identify the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in patients with transthyretin (ATTR) amyloidosis. PATIENTS AND METHODS: We performed a retrospective analysis of patients with biopsy-proven ATTRwt (wild-type transthyretin amyloid protein) and genopositive ATTR V122I (valine-to-isoleucine substitution at position 122 of the TTR gene) amyloidosis evaluated at the Amyloidosis Center at Boston University and Boston Medical Center between 1 January 2003 and 31 December 2016...
February 9, 2018: Amyloid: the International Journal of Experimental and Clinical Investigation
https://www.readbyqxmd.com/read/29416776/monoclonal-gammopathy-of-renal-significance-mgrs-increases-the-risk-for-progression-to-multiple-myeloma-an-observational-study-of-2935-mgus-patients
#18
Normann Steiner, Georg Göbel, Patricia Suchecki, Wolfgang Prokop, Hannes Neuwirt, Eberhard Gunsilius
Purpose: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignancy preceding multiple myeloma (MM) or related disorders. In MGUS, renal impairment caused by deposition of the monoclonal immunoglobulins or free light-chains monoclonal gammopathy of renal significance (MGRS) is often associated with high morbidity and mortality. We analysed the prevalence of renal impairment, clinical features and the long-term outcome in 2935 patients with MGUS. Methods: Between 1/2000 and 8/2016, 2935 adult patients with MGUS were identified in our database...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29390260/paraproteinemic-keratopathy-in-monoclonal-gammopathy-of-undetermined-significance-treated-with-primary-keratoprosthesis-case-report-histopathologic-findings-and-world-literature-review
#19
Homer H Chiang, Rebekah S Wieland, Thomas S Rogers, Pamela C Gibson, George Atweh, Gregory McCormick
RATIONALE: We report a case of paraproteinemic keratopathy associated with monoclonal gammopathy of undetermined significance, treated with keratoprosthesis as a primary penetrating procedure. Histopathological findings and a world literature review are presented. PATIENT CONCERNS: A 74 year old female recently diagnosed with monoclonal gammopathy undetermined significance presented with progressive blurry vision bilaterally. DIAGNOSES: Examination revealed corneal opacities consistent with paraproteinemic keratopathy...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29389935/novel-pedigree-analysis-implicates-dna-repair-and-chromatin-remodeling-in-multiple-myeloma-risk
#20
Rosalie G Waller, Todd M Darlington, Xiaomu Wei, Michael J Madsen, Alun Thomas, Karen Curtin, Hilary Coon, Venkatesh Rajamanickam, Justin Musinsky, David Jayabalan, Djordje Atanackovic, S Vincent Rajkumar, Shaji Kumar, Susan Slager, Mridu Middha, Perrine Galia, Delphine Demangel, Mohamed Salama, Vijai Joseph, James McKay, Kenneth Offit, Robert J Klein, Steven M Lipkin, Charles Dumontet, Celine M Vachon, Nicola J Camp
The high-risk pedigree (HRP) design is an established strategy to discover rare, highly-penetrant, Mendelian-like causal variants. Its success, however, in complex traits has been modest, largely due to challenges of genetic heterogeneity and complex inheritance models. We describe a HRP strategy that addresses intra-familial heterogeneity, and identifies inherited segments important for mapping regulatory risk. We apply this new Shared Genomic Segment (SGS) method in 11 extended, Utah, multiple myeloma (MM) HRPs, and subsequent exome sequencing in SGS regions of interest in 1063 MM / MGUS (monoclonal gammopathy of undetermined significance-a precursor to MM) cases and 964 controls from a jointly-called collaborative resource, including cases from the initial 11 HRPs...
February 2018: PLoS Genetics
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