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https://www.readbyqxmd.com/read/28943951/recurrent-alterations-of-the-ww-domain-containing-oxidoreductase-gene-spanning-the-common-fragile-site-fra16d-in-multiple-myeloma-and-monoclonal-gammopathy-of-undetermined-significance
#1
Hiroshi Handa, Yoshiko Sasaki, Hikaru Hattori, Lobna Alkebsi, Tetsuhiro Kasamatsu, Takayuki Saitoh, Takeki Mitsui, Akihiko Yokohama, Norifumi Tsukamoto, Morio Matsumoto, Hirokazu Murakami
The putative tumor suppressor gene WW domain containing oxidoreductase (WWOX) spans a common fragile site (CFS) on chromosome 16q23.3. CFSs are regions of profound genomic instability and sites for genomic deletions in cancer cells. Therefore, WWOX is structurally altered in diverse nonhematological cancer types. However, the function of WWOX in hematological tumor types, including multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) remains unclear. WWOX expression and methylation in patients with MM, MGUS, or noninvasive lymphoma (control) were analyzed using reverse transcription- and methylation specific-polymerase chain reaction analysis...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28943924/network-based-analysis-of-the-molecular-mechanisms-of-multiple-myeloma-and-monoclonal-gammopathy-of-undetermined-significance
#2
Zhi Liu, Jing Huang, Qi Zhong, Yanling She, Ruimin Ou, Cheng Li, Rui Chen, Mengdong Yao, Qing Zhang, Shuang Liu
The present study aimed to reveal the molecular mechanisms of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). This was a secondary study on microarray dataset GSE80608, downloaded from the Gene Expression Omnibus database, which included 10 control samples, 10 MGUS samples and 10 MM samples. Differentially expressed genes (DEGs) were identified between control and MGUS samples, and between control and MM samples. A protein-protein interaction (PPI) network was built for studying the interactions between the DEGs...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28915587/expression-and-release-of-glucose-regulated-protein-78-grp78-in-multiple-myeloma
#3
Normann Steiner, Bojana Borjan, Roman Hajek, Karin Jöhrer, Georg Göbel, Wolfgang Willenbacher, Johann Kern, Eberhard Gunsilius, Gerold Untergasser
INTRODUCTION: Multiple myeloma (MM) is a plasma cell neoplasm that is mostly incurable due to acquired resistance during the treatment course. Thus, we evaluated expression and release of glucose-regulated protein 78 kDa (GRP78/BiP), an endoplasmic reticulum (ER) based pro-survival chaperone involved in immunoglobulin folding and unfolded protein responses. RESULTS: GRP78 protein expression in the ER and on the cell surface did not significantly differ between MGUS, NDMM and RRMM patients although there was a trend to higher surface expression in RRMM...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903571/asymptomatic-and-treatment-requiring-multiple-myeloma-data-from-the-czech-registry-of-monoclonal-gammopathies
#4
L Brozova, J Jarkovský, L Pour, J Minárik, A Jungová, E Gregora, I Spicka, V Maisnar, R Hájek
BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) and smouldering multiple myeloma (SMM) are premalignant stages of multiple myeloma (MM). MM is a malignancy of plasma cells, which is associated with a median overall survival of 5 to 7 years. MM accounts for approximately 10% of hematological malignancies. PATIENTS AND METHODS: Descriptive analysis of data from 19 Czech centres collected in the Registry of Monoclonal Gammopathies (RMG) was performed...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28903570/czech-registry-of-monoclonal-gammopathies-technical-solution-data-collection-and-visualisation
#5
L Brozova, D Schwarz, I Snabl, J Kalina, B Pavlickova, M Komenda, J Jarkovský, P Němec, D Horinek, Z Stefanikova, L Pour, R Hájek, V Maisnar
BACKGROUND: The Registry of Monoclonal Gammopathies (RMG) was established by the Czech Myeloma Group in 2007. RMG is a registry designed for the collection of clinical data concerning diagnosis, treatment, treatment results and survival of patients with monoclonal gammopathies. Data on patients with monoclonal gammopathy of undetermined significance (MGUS), Waldenström macroglobulinaemia (WM), multiple myeloma (MM) or primary AL ("amyloid light-chain") amyloidosis are collected in the registry...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28886228/the-serum-heavy-light-chain-immunoassay-a-valuable-tool-for-sensitive-paraprotein-assessment-risk-and-disease-monitoring-in-monoclonal-gammopathies
#6
Christine Greil, Gabriele Ihorst, Felix Gaiser, Ulrich Salzer, Emanuel Bisse, Efstathios Kastritis, Heinz Ludwig, Ralph Wäsch, Monika Engelhardt
OBJECTIVE: The heavy/light chain (HLC)-immunoassay quantifies light chain types of each immunoglobulin class in patients with monoclonal gammopathies. METHODS: We assessed 147 consecutive patients with different forms and stages of plasma cell dyscrasias (PCD) who received standard tests (serum and urine protein electrophoresis [SPEP, UPEP], immunofixation [IFE], serum free light chain [SFLC]) and HLC-immunoassay. Patients with multiple myeloma (MM, n=102), smoldering MM (SMM, n=5), monoclonal gammopathy of undetermined significance (MGUS, n=28) and waldenström's macroglobulinemia (WM, n=12) were included...
September 8, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28806822/-multiple-myeloma-current-status-in-diagnostic-testing-and-therapy
#7
Michael Kehrer, Sebastian Koob, Andreas Strauss, Dieter Christian Wirtz, Jan Schmolders
Background Multiple myeloma is a haematological blood cancer of the bone marrow and is classified by the World Health Organisation (WHO) as a plasma cell neoplasm. In multiple myeloma, normal plasma cells transform into malignant myeloma cells and produce large quantities of an abnormal immunoglobulin called monoclonal protein or M protein. This ultimately causes multiple myeloma symptoms such as bone damage or kidney problems. The annual worldwide incidence of multiple myeloma is estimated to be 6 - 7/100,000 and accounts for 1% of all cancer...
August 14, 2017: Zeitschrift Für Orthopädie und Unfallchirurgie
https://www.readbyqxmd.com/read/28792255/host-related-immunodeficiency-in-the-development-of-multiple-myeloma
#8
Talib Dosani, Sham Mailankody, Neha Korde, Elisabet Manasanch, Manisha Bhutani, Nishant Tageja, Mark Roschewski, Mary Kwok, Dickran Kazandjian, Rene Costello, Debra Burton, Yong Zhang, David Liewehr, Seth M Steinberg, Irina Maric, Ola Landgren
Host-related immunodeficiency is known to play a role in the development of multiple myeloma (MM) from its precursor conditions (monoclonal gammopathy of undetermined significance, MGUS, smoldering multiple myeloma, SMM). In order to understand the underlying immune changes in this process, we characterized immune patterns from MGUS to SMM to MM. We further sought to identify potential novel immune biomarkers that may predict progression of SMM to MM. We characterized patterns of circulating lymphocytes in 181 patients using multiparametric flow cytometry...
August 9, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28766001/dynamic-contrast-enhanced-magnetic-resonance-imaging-parameters-correlate-with-advanced-revised-iss-and-angiopoietin-1-angiopoietin-2-ratio-in-patients-with-multiple-myeloma
#9
Evangelos Terpos, Dimitris Matsaridis, Vassilis Koutoulidis, Flora Zagouri, Dimitrios Christoulas, Sophia Fontara, Evangelia Panourgias, Maria Gavriatopoulou, Efstathios Kastritis, Meletios A Dimopoulos, Lia A Moulopoulos
The aim of the study was to assess the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with newly diagnosed multiple myeloma (MM) who were treated with novel anti-myeloma agents. We studied 60 previously untreated MM patients at diagnosis, 14 with smoldering MM (SMM) and 5 with MGUS. All patients underwent MRI of the thoracolumbar spine and pelvis before the administration of any kind of therapy, and DCE-MRI was performed. The MRI perfusion parameters evaluated were wash-in (WIN), washout (WOUT), time-to-peak (TTPK), time-to-maximum slope (TMSP), and the WIN/TMSP ratio...
August 1, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28731904/monoclonal-gammopathy-of-undetermined-significance-after-kidney-transplantation-single-center-experience
#10
Gaetano Alfano, Francesco Fontana, Elisabetta Colaci, Andrea Messerotti, Francesca Bettelli, Leonardo Potenza, Mario Luppi, Gianni Cappelli
BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant plasma cell disorder. Prevalence and clinical outcomes of MGUS in kidney transplant (KT) recipients have been previously reported in few studies with conflicting results. METHODS: We conducted a retrospective study in a population of 548 KT recipients transplanted between 1998 and 2015. RESULTS: Thirty-nine subjects (8.1%) developed MGUS after KT...
July 21, 2017: Transplantation
https://www.readbyqxmd.com/read/28728165/active-multiple-myeloma-suppresses-and-typically-eliminates-coexisting-mgus
#11
John P Campbell, Jennifer L J Heaney, Sankalp Pandya, Zaheer Afzal, Martin Kaiser, Roger Owen, J Anthony Child, Walter Gregory, Gareth J Morgan, Graham H Jackson, Chris M Bunce, Mark T Drayson
BACKGROUND: Myeloma is consistently preceded by premalignant monoclonal gammopathy of undetermined significance (MGUS). In >5% of MGUS patients there is a second MGUS clone (biclonal gammopathy of undetermined significance; BGUS), yet, at myeloma diagnosis, presentation of biclonal gammopathy myeloma (BGMy) is considered less frequent, implying that myeloma eradicates coexisting MGUS. METHODS: In the largest study of its kind, we assessed BGMy frequency amongst 6399 newly diagnosed myeloma patients enrolled in recent UK clinical trials...
September 5, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28727816/high-levels-of-flt3-ligand-in-bone-marrow-and-peripheral-blood-of-patients-with-advanced-multiple-myeloma
#12
Normann Steiner, Roman Hajek, Sabina Sevcikova, Bojana Borjan, Karin Jöhrer, Georg Göbel, Gerold Untergasser, Eberhard Gunsilius
INTRODUCTION: Multiple myeloma (MM) is still incurable due to resistance against various therapies. Thus, the identification of biomarkers predicting progression is urgently needed. Here, we evaluated four biomarkers in bone marrow and peripheral blood of MM patients for their prognostic significance. MATERIALS & METHODS: Bone marrow- and peripheral blood plasma levels of FLT3-L, soluble TIE2, endostatin, and osteoactivin were determined in patients with monoclonal gammopathy of undetermined significance (MGUS, n = 14/n = 4), patients with newly diagnosed MM (NDMM, n = 42/n = 31) and patients with relapsed/refractory MM (RRMM, n = 27/n = 16) by sandwich ELISA...
2017: PloS One
https://www.readbyqxmd.com/read/28706164/clinicopathological-significance-of-the-p16-hypermethylation-in-multiple-myeloma-a-systematic-review-and-meta-analysis
#13
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)...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28673317/the-ubiquitin-conjugating-enzyme-ube2o-modulates-c-maf-stability-and-induces-myeloma-cell-apoptosis
#14
Yujia Xu, Zubin Zhang, Jie Li, Jiefei Tong, Biyin Cao, Paul Taylor, Xiaowen Tang, Depei Wu, Michael F Moran, Yuanying Zeng, Xinliang Mao
BACKGROUND: UBE2O is proposed as a ubiquitin-conjugating enzyme, but its function was largely unknown. METHODS: Mass spectrometry was applied to identify c-Maf ubiquitination-associated proteins. Immunoprecipitation was applied for c-Maf and UBE2O interaction. Immunoblotting was used for Maf protein stability. Luciferase assay was used for c-Maf transcriptional activity. Lentiviral infections were applied for UBE2O function in multiple myeloma (MM) cells. Flow cytometry and nude mice xenografts were applied for MM cell apoptosis and tumor growth assay, respectively...
July 3, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28602036/circulating-adiponectin-levels-differ-between-patients-with-multiple-myeloma-and-its-precursor-disease
#15
Jonathan N Hofmann, Sham Mailankody, Neha Korde, Ye Wang, Nishant Tageja, Rene Costello, Adriana Zingone, Malin Hultcrantz, Michael N Pollak, Mark P Purdue, Ola Landgren
OBJECTIVE: An increased risk of multiple myeloma (MM) has been observed among individuals with low prediagnostic circulating levels of adiponectin, a metabolic hormone that is typically underexpressed among those with overweight or obesity. To assess whether adiponectin may influence myeloma development or progression to frank MM, circulating adiponectin levels were compared across patients with different stages of MM and its precursor, monoclonal gammopathy of undetermined significance (MGUS)...
June 11, 2017: Obesity
https://www.readbyqxmd.com/read/28550183/somatic-mutation-spectrum-in-monoclonal-gammopathy-of-undetermined-significance-indicates-a-less-complex-genomic-landscape-compared-to-multiple-myeloma
#16
Aneta Mikulasova, Christopher P Wardell, Alexander Murison, Eileen M Boyle, Graham H Jackson, Jan Smetana, Zuzana Kufova, Ludek Pour, Viera Sandecka, Martina Almasi, Pavla Vsianska, Evzen Gregora, Petr Kuglik, Roman Hajek, Faith E Davies, Gareth J Morgan, Brian A Walker
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant precursor of multiple myeloma with a 1% risk of progression per year. Although targeted analyses have shown the presence of specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS genes mutations, little is known about the molecular mechanism of malignant transformation. We have performed whole exome sequencing together with CGH+SNP array analysis in 33 flow-cytometry separated abnormal plasma cell samples from MGUS patients to describe somatic gene mutations and chromosome changes at the genome-wide level...
May 26, 2017: Haematologica
https://www.readbyqxmd.com/read/28540748/expression-of-the-il-6-receptor-alpha-chain-cd126-in-normal-and-abnormal-plasma-cells-in-monoclonal-gammopathy-of-undetermined-significance-and-smoldering-myeloma
#17
Dalia Abdel-Raouf Salem, Neha Korde, David J Venzon, David J Liewehr, Irina Maric, Katherine R Calvo, Raul Braylan, Prashant R Tembhare, Constance M Yuan, Carl Ola Landgren, Maryalice Stetler-Stevenson
IL-6 activity in normal plasma cells (nPCs) and abnormal plasma cells (aPCs) is CD126 (subunit of IL-6 receptor) dependent. We quantified CD126 expression on nPCs and aPCs in monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma (SMM), and multiple myeloma (MM). CD126 was detected on all nPCs and aPCs indicating that CD126 does not have diagnostic utility. CD126 expression was higher in aPCs than in nPCs in 85% SMM but only 41% MGUS and there was evidence that CD126 was higher in aPCs than nPCs in the SMM (p = ...
May 25, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28508985/light-chain-fanconi-syndrome-in-a-patient-with-acute-myeloid-leukemia-and-monoclonal-gammopathy-of-undetermined-significance
#18
Daniel W Ross, Rimda Wanchoo, Adriana Guigova, Cristina Ghiuzeli, Steven L Allen, Kenar D Jhaveri
Proximal tubules are a target for paraproteinemic diseases. Cast nephropathy, light chain deposition diseases, and amyloidosis are frequently encountered in patients with multiple myeloma. Rarely, a subset of patients develop light chain Fanconi syndrome (LCFS). LCFS has been reported with multiple myeloma, monoclonal gammopathy of renal significance (MGRS), chronic lymphocytic leukemia, Waldenstrom's macroglobulinemia and diffuse large B-cell lymphoma. No cases have been described with other hematologic malignancies...
November 2016: CEN Case Reports
https://www.readbyqxmd.com/read/28502031/vitamin-d-and-plasma-cell-dyscrasias-reviewing-the-significance
#19
REVIEW
Nicholas Burwick
Monoclonal gammopathy of undetermined significance (MGUS) is a clonal plasma cell disorder and precursor disease to multiple myeloma and other related cancers. While MGUS is considered a benign disorder, with a low risk of disease progression, patients have altered bone microarchitecture and an increased risk of bone fracture. In addition, alterations in immune function are regularly found to correlate with disease activity. Vitamin D, an important hormone for bone and immune health, is commonly deficient in multiple myeloma patients...
August 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28493835/expression-and-release-of-glucose-regulated-protein-78-grp78-in-multiple-myeloma
#20
Normann Steiner, Bojana Borjan, Roman Hajek, Karin Jöhrer, Georg Göbel, Wolfgang Willenbacher, Johann Kern, Eberhard Gunsilius, Gerold Untergasser
INTRODUCTION: Multiple myeloma (MM) is a plasma cell neoplasm that is mostly incurable due to acquired resistance during the treatment course. Thus, we evaluated expression and release of glucose-regulated protein 78 kDa (GRP78/BiP), an endoplasmic reticulum (ER) based pro-survival chaperone involved in immunoglobulin folding and unfolded protein responses. RESULTS: GRP78 protein expression in the ER and on the cell surface did not significantly differ between MGUS, NDMM and RRMM patients although there was a trend to higher surface expression in RRMM...
April 21, 2017: Oncotarget
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