Read by QxMD icon Read

, multiple myeloma, MGUS

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
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
Sevgi Kalayoglu-Besisik
Hyperviscosity syndrome (HVS) develops most commonly in Waldenström's macroglobulinemia (WM) and multiple myeloma (MM). Plasmapheresis is the immediate therapy and very effective at relieving symptoms by removing paraprotein. The most commonly used replacement fluid is 4%-5% human albumin in physiologic saline. FFP may be used in patients with coagulation abnormalities. Plasmapheresis should be continued until acute symptoms abate. Hyperviscosity impairs the circulation in the retina and causes hemorrhages around the small retinal vessels...
February 20, 2018: Transfusion and Apheresis Science
Charlotte Pawlyn, Andrea Loehr, Cody Ashby, Ruslana Tytarenko, Shayu Deshpande, James Sun, Kyle Fedorchak, Tariq Mughal, Faith E Davies, Brian A Walker, Gareth J Morgan
PARP inhibitors can induce synthetic lethality in tumors characterized by homologous recombination deficiency (HRD), which can be detected by evaluating genome-wide loss of heterozygosity (LOH). Multiple myeloma (MM) is a genetically unstable tumor and we hypothesized that HRD-related LOH (HRD-LOH) could be detected in patient samples, supporting a potential role for PARP inhibition in MM. Using results from targeted next-generation sequencing studies (FoundationOne® Heme), we analyzed HRD-LOH in patients at all disease stages (MGUS (n = 7), smoldering MM (SMM, n = 30), newly diagnosed MM (NDMM, n = 71), treated MM (TRMM, n = 64), and relapsed MM (RLMM, n = 234)) using an algorithm to identify HRD-LOH segments...
February 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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
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
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
Po-Chang Hsu, Shyi-Jou Chen
RATIONALE: The serum and urine-free light chain (sFLC/uFLC) ratios of kappa (κ) to lambda (λ) serve as biomarkers for plasma cell disorders, especially multiple myeloma. However, to our best knowledge, the ratios have not been appropriately assessed for acute transverse myelitis (ATM). PATIENT CONCERNS: We present a 12-year-old boy who had sudden onset low back pain following paralysis of his 4 extremities and disturbance consciousness. Magnetic resonance imaging (MRI) of the brain and spine indicated diffuse hyperintensity in T2-weighted images from the cervical spinal cord to the conus medullaris...
December 2017: Medicine (Baltimore)
Joyce W Kamande, Maria A M Lindell, Małgorzata A Witek, Peter M Voorhees, Steven A Soper
Blood samples from patients with plasma cell disorders were analysed for the presence of circulating plasma cells (CPCs) using a microfluidic device modified with monoclonal anti-CD138 antibodies. CPCs were immuno-phenotyped using a CD38/CD56/CD45 panel and identified in 78% of patients with monoclonal gammopathy of undetermined significance (MGUS), all patients with smouldering and symptomatic multiple myeloma (MM), and none in the controls. The burden of CPCs was higher in patients with symptomatic MM compared with MGUS and smouldering MM (p < 0...
January 26, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Sonia Vallet, Nicholas R Hoyle, Robert A Kyle, Klaus Podar, Martin Pecherstorfer
Multiple myeloma (MM) is characterized by bone lesions arising due to unbalanced bone remodeling. Changes in the bone formation marker amino-terminal propeptide of type I collagen (PINP) and the bone resorption marker β-CrossLaps (CTX) reflect physiologic bone turnover. Whether PINP and CTX have a role in disease progression from monoclonal gammopathy of undetermined significance (MGUS) to MM is unknown. In this cross-sectional follow-up study, 241 patients with MM or MGUS were included. Serum levels of PINP and CTX were significantly higher in MM patients compared to MGUS...
January 18, 2018: Leukemia & Lymphoma
Robert A Kyle, Dirk R Larson, Terry M Therneau, Angela Dispenzieri, Shaji Kumar, James R Cerhan, S Vincent Rajkumar
BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) occurs in approximately 3% of persons 50 years of age or older. METHODS: We studied 1384 patients who were residing in southeastern Minnesota and in whom MGUS was diagnosed at the Mayo Clinic in the period from 1960 through 1994; the median follow-up was 34.1 years (range, 0.0 to 43.6). The primary end point was progression to multiple myeloma or another plasma-cell or lymphoid disorder. RESULTS: During 14,130 person-years of follow-up, MGUS progressed in 147 patients (11%), a rate that was 6...
January 18, 2018: New England Journal of Medicine
M Schmalzing, H-P Tony, S Knop
In rheumatological practice monoclonal gammopathy of undetermined significance (MGUS) is a common incidental finding. Several rheumatic inflammatory diseases are known to have an elevated risk of MGUS, which can evolve into multiple myeloma or other lymphatic malignancies. The relevant definitions of disease entities are described, as well as algorithms for further diagnostic work-up and follow-up for monoclonal gammopathy, depending on the risk of progression. Therapeutic strategies against multiple myeloma are presented...
October 2017: Zeitschrift Für Rheumatologie
Roberto Ria, Franco Dammacco, Angelo Vacca
The heavy chain diseases (HCDs) are rare B-cell malignancies characterized by the production of a monoclonal immunoglobulin heavy chain without an associated light chain. There are three types of HCD, defined by the class of immunoglobulin heavy chain produced: IgA (α-HCD), IgG (γ-HCD), and IgM (μ-HCD). Alpha-HCD is the most common and usually occurs as intestinal malabsorption in a young adult from a country of the Mediterranean area. Gamma- and μ-HCDs are rarer and associated with a B-cell non-Hodgkin lymphoma that produces an abnormal Ig heavy chain...
2018: Mediterranean Journal of Hematology and Infectious Diseases
Irene M Ghobrial, Alexandre Detappe, Kenneth C Anderson, David P Steensma
Several haematological malignancies, including multiple myeloma (MM) and acute myeloid leukaemia (AML), have well-defined precursor states that precede the development of overt cancer. MM is almost always preceded by monoclonal gammopathy of undetermined significance (MGUS), and at least a quarter of all patients with myelodysplastic syndromes (MDS) have disease that evolves into AML. In turn, MDS are frequently anteceded by clonal haematopoiesis of indeterminate potential (CHIP). The acquisition of additional genetic and epigenetic alterations over time clearly influences the increasingly unstable and aggressive behaviour of neoplastic haematopoietic clones; however, perturbations in the bone-marrow microenvironment are increasingly recognized to have key roles in initiating and supporting oncogenesis...
January 9, 2018: Nature Reviews. Clinical Oncology
Marianna Thordardottir, Ebba K Lindqvist, Sigrun H Lund, Rene Costello, Debra Burton, Neha Korde, Sham Mailankody, Gudny Eiriksdottir, Lenore J Launer, Vilmundur Gudnason, Tamara B Harris, Ola Landgren, Sigurdur Y Kristinsson
All multiple myeloma (MM) cases are preceded by the premalignant state monoclonal gammopathy of undetermined significance (MGUS). Results from previous studies show a positive association between obesity and MM; however, the association between obesity and MGUS is controversial. The aims were to determine (1) if obesity is associated with an increased risk of MGUS and light-chain MGUS (LC-MGUS) and (2) whether obesity is associated with a higher risk of progression to MM and other lymphoproliferative (LP) diseases...
November 14, 2017: Blood Advances
Zhenhai Li, Kwan Yeung Wong, Godfrey Chi-Fung Chan, Wee-Joo Chng, Chor Sang Chim
miR-342-3p, localized to 14q32, is a tumor suppressor miRNA implicated in multiple cancers. As the promoter region of its host gene, EVL, is embedded in a CpG island, we postulated that miR-342-3p is an intronic miRNA co-regulated with its host gene by promoter DNA methylation in multiple myeloma (MM). By methylation-specific polymerase chain reaction, verified by quantitative bisulfite pyrosequencing, methylation of EVL/miR-342 was absent in all healthy controls (n = 10) and 12 of 15 (80%) human myeloma cell lines (HMCLs), but partially methylated in 3 of 15 (20%) HMCLs, including KMS-12-PE, OCI-MY5, and RPMI-8226R...
November 23, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
Ronald S Go, S Vincent Rajkumar
Monoclonal gammopathy of undetermined significance (MGUS) is, in many ways, a unique hematologic entity. Unlike most hematologic conditions in which the diagnosis is intentional and credited to hematologists, the discovery of MGUS is most often incidental and made by nonhematologists. MGUS is considered an obligate precursor to several lymphoplasmacytic malignancies, including immunoglobulin light-chain amyloidosis, multiple myeloma, and Waldenström macroglobulinemia. Therefore, long-term follow-up is generally recommended...
January 11, 2018: Blood
John P Campbell, Jennifer L J Heaney, Sankalp Pandya, Zaheer Afzal, Martin Kaiser, Roger Owen, J Anthony Child, David A Cairns, Walter Gregory, Gareth J Morgan, Graham H Jackson, Chris M Bunce, Mark T Drayson
BACKGROUND: Multiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS), which is usually only treated by a form of anti-multiple myeloma therapy if it is causing substantial disease through deposition of secreted M proteins. However, studies comparing how MGUS and multiple myeloma plasma cell clones respond to these therapies are scarce. Biclonal gammopathy multiple myeloma is characterised by the coexistence of an active multiple myeloma clone and a benign MGUS clone, and thus provides a unique model to assess the responses of separate clones to the same anti-multiple myeloma therapy, in the same patient, at the same time...
December 2017: Lancet Haematology
Huiqing Yu, Liejun Yang, Yunfeng Fu, Meng Gao, Ling Tian
It is well known that the loss of function of the p16INK4A gene is mainly caused by the hypermethylation of the p16 gene; however, whether or not the inactivation is associated with the clinical significance of multiple myeloma (MM) remains elusive. A meta-analysis was conducted to quantitatively determine the role of the p16 hypermethylation in the clinical significance of MM. We demonstrated that MM patients show much higher hypermethylation rates on the p16 gene in bone marrow compared to normal individuals, as well as monoclonal gammopathy of undetermined significance (MGUS)...
October 10, 2017: Oncotarget
Adrien Bosseboeuf, Sophie Allain-Maillet, Nicolas Mennesson, Anne Tallet, Cédric Rossi, Laurent Garderet, Denis Caillot, Philippe Moreau, Eric Piver, François Girodon, Hélène Perreault, Sophie Brouard, Arnaud Nicot, Edith Bigot-Corbel, Sylvie Hermouet, Jean Harb
Multiple myeloma (MM) and its pre-cancerous stage monoclonal gammopathy of undetermined significance (MGUS) allow to study immune responses and the chronology of inflammation in the context of blood malignancies. Both diseases are characterized by the production of a monoclonal immunoglobulin (mc Ig) which for subsets of MGUS and MM patients targets pathogens known to cause latent infection, a major cause of inflammation. Inflammation may influence the structure of both polyclonal (pc) Ig and mc Ig produced by malignant plasma cells via the sialylation of Ig Fc fragment...
2017: Frontiers in Immunology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"