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smoldering multiple myeloma

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https://www.readbyqxmd.com/read/29326807/heavy-chain-diseases-and-myeloma-associated-fanconi-syndrome-an-update
#1
REVIEW
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
https://www.readbyqxmd.com/read/29321378/glutamine-derived-2-hydroxyglutarate-is-associated-with-disease-progression-in-plasma-cell-malignancies
#2
Wilson I Gonsalves, Vijay Ramakrishnan, Taro Hitosugi, Toshi Ghosh, Dragan Jevremovic, Tumpa Dutta, Dhananjay Sakrikar, Xuan-Mai Petterson, Linda Wellik, Shaji K Kumar, K Sreekumaran Nair
The production of the oncometabolite 2-hydroxyglutarate (2-HG) has been associated with c-MYC overexpression. c-MYC also regulates glutamine metabolism and drives progression of asymptomatic precursor plasma cell (PC) malignancies to symptomatic multiple myeloma (MM). However, the presence of 2-HG and its clinical significance in PC malignancies is unknown. By performing 13C stable isotope resolved metabolomics (SIRM) using U[13C6]Glucose and U[13C5]Glutamine in human myeloma cell lines (HMCLs), we show that 2-HG is produced in clonal PCs and is derived predominantly from glutamine anaplerosis into the TCA cycle...
January 11, 2018: JCI Insight
https://www.readbyqxmd.com/read/29296837/baseline-mutational-patterns-and-sustained-mrd-negativity-in-patients-with-high-risk-smoldering-myeloma
#3
Sham Mailankody, Dickran Kazandjian, Neha Korde, Mark Roschewski, Elisabet Manasanch, Manisha Bhutani, Nishant Tageja, Mary Kwok, Yong Zhang, Adriana Zingone, Laurence Lamy, Rene Costello, Candis Morrison, Malin Hultcrantz, Austin Christofferson, Megan Washington, Martin Boateng, Seth M Steinberg, Maryalice Stetler-Stevenson, William D Figg, Elli Papaemmanuil, Wyndham H Wilson, Jonathan J Keats, Ola Landgren
Early results of a prospective phase 2 clinical trial of carfilzomib, lenalidomide, and dexamethasone followed by lenalidomide maintenance in high-risk smoldering myeloma showed promising results that were previously published. Here, we provide novel insights into the genetic landscape of high-risk smoldering myeloma and information on sustained minimal residual disease (MRD) negativity with an expanded cohort of patients. Eighteen patients with high-risk smoldering myeloma were enrolled between 29 May 2012, and 14 January 2014...
October 10, 2017: Blood Advances
https://www.readbyqxmd.com/read/29222256/shall-we-treat-smoldering-multiple-myeloma-in-the-near-future
#4
REVIEW
Ola Landgren
In recent years, several new drugs have been approved for the treatment of multiple myeloma. Many of these newer drugs are highly efficacious and less toxic than older chemotherapy drugs. In 2014, the diagnostic criteria for multiple myeloma were revised. The intent with the new criteria was to identify patients who require therapy at an earlier stage than at manifestation of organ complications. A subset of patients who were previously defined as having high-risk smoldering multiple myeloma was redefined as having multiple myeloma...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29159320/immunogenicity-and-persistence-of-the-13-valent-pneumococcal-conjugate-vaccine-pcv13-in-patients-with-untreated-smoldering-multiple-myeloma-smm-a-pilot-study
#5
Mathilde Bahuaud, Hélène Bodilis, Marion Malphettes, Anaïs Maugard Landre, Caroline Matondo, Didier Bouscary, Frédéric Batteux, Odile Launay, Jean-Paul Fermand
Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder that frequently progress to multiple myeloma (MM), a disease at high risk of pneumococcal infections. Moreover, if the polysaccharide vaccine is poorly immunogenic in MM, the 13-valent conjugated vaccine has never been tested in clonal plasma cell disorders. We evaluated its immunogenicity for 7 serotypes in 20 patients ≥ 50 years of age with smoldering multiple myeloma (SMM) pre and post routine-vaccination with PCV13. Concentrations of IgG specific for 7 serotypes were measured at baseline, 1, 6, and 12 months after vaccination by standardized ELISA and an Opsonophagocytic Assay (OPA)...
November 2017: Heliyon
https://www.readbyqxmd.com/read/29118010/cd38-antibodies-in-multiple-myeloma-back-to-the-future
#6
Niels W C J van de Donk, Paul G Richardson, Fabio Malavasi
CD38 is highly and uniformly expressed on MM cells, and at relatively low levels on normal lymphoid and myeloid cells, and in some tissues of non-hematopoietic origin. CD38 is a transmembrane glycoprotein with ectoenzymatic activity, and also functions as receptor and adhesion molecule. Altogether, this has triggered the development of several CD38 antibodies including daratumumab (fully human), isatuximab (chimeric), and MOR202 (fully human). CD38 antibodies have pleiotropic mechanisms of action including Fc-dependent immune effector mechanisms, direct apoptotic activity, and immunomodulatory effects by the elimination of CD38-positive immunesuppressor cells...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29040254/when-to-initiate-treatment-in-smoldering-multiple-myeloma
#7
María-Victoria Mateos
No abstract text is available yet for this article.
October 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29031125/low-protein-z-levels-in-patients-with-plasma-cell-neoplasms-are-inversely-correlated-with-il-6-levels
#8
O Gutwein, N Rahimi-Levene, K Herzog-Tzarfati, O Garach-Jehoshua, A Nagler, M Izak, M Koren-Michowitz
Patients with multiple myeloma (MM) have an increased thrombotic risk, but pathogenesis remains uncertain. Low levels of Protein Z (PZ), a vitamin K-dependent plasma protein, are associated with venous as well as arterial thrombosis. The purpose of this study was to analyze PZ levels in patients with plasma cell neoplasms. PATIENTS AND METHODS: The study consisted of 64 plasma cells neoplasm patients and 42 healthy individuals. Clinical investigations included measurement of plasma PZ and IL-6 levels...
November 2017: Leukemia Research
https://www.readbyqxmd.com/read/28978808/monoclonal-igg-in-mgus-and-multiple-myeloma-targets-infectious-pathogens
#9
Adrien Bosseboeuf, Delphine Feron, Anne Tallet, Cédric Rossi, Cathy Charlier, Laurent Garderet, Denis Caillot, Philippe Moreau, Marina Cardó-Vila, Renata Pasqualini, Wadih Arap, Alfreda Destea Nelson, Bridget S Wilson, Hélène Perreault, Eric Piver, Pierre Weigel, François Girodon, Jean Harb, Edith Bigot-Corbel, Sylvie Hermouet
Subsets of mature B cell neoplasms are linked to infection with intracellular pathogens such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), or Helicobacter pylori. However, the association between infection and the immunoglobulin-secreting (Ig-secreting) B proliferative disorders remains largely unresolved. We investigated whether the monoclonal IgG (mc IgG) produced by patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM) targets infectious pathogens...
October 5, 2017: JCI Insight
https://www.readbyqxmd.com/read/28969692/role-of-protein-kinases-ck1%C3%AE-and-ck2-in-multiple-myeloma-regulation-of-pivotal-survival-and-stress-managing-pathways
#10
REVIEW
Sabrina Manni, Marilena Carrino, Francesco Piazza
Multiple myeloma (MM) is a malignant tumor of transformed plasma cells. MM pathogenesis is a multistep process. This cancer can occur de novo (rarely) or it can develop from monoclonal gammopathy of undetermined significance (most of the cases). MM can be asymptomatic (smoldering myeloma) or clinically active. Malignant plasma cells exploit intrinsic and extrinsic bone marrow microenvironment-derived growth signals. Upregulation of stress-coping pathways is also instrumental to maintain MM cell growth. The phylogenetically related Ser/Thr kinases CSNK1A1 (CK1α) and CSNK2 (CK2) have recently gained a growing importance in hematologic malignancies arising both from precursors and from mature blood cells...
October 2, 2017: Journal of Hematology & Oncology
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
#11
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/28841211/whole-body-computed-tomography-versus-conventional-skeletal-survey-in-patients-with-multiple-myeloma-a-study-of-the-international-myeloma-working-group
#12
J Hillengass, L A Moulopoulos, S Delorme, V Koutoulidis, J Mosebach, T Hielscher, M Drake, S V Rajkumar, B Oestergaard, N Abildgaard, M Hinge, T Plesner, Y Suehara, K Matsue, N Withofs, J Caers, A Waage, H Goldschmidt, M A Dimopoulos, S Lentzsch, B Durie, E Terpos
For decades, conventional skeletal survey (CSS) has been the standard imaging technique for multiple myeloma (MM). However, recently whole-body computed tomography (WBCT) has been implemented into the diagnostic criteria of MM. This analysis compares sensitivity and prognostic significance of WBCT and CSS in patients with smoldering MM (SMM) and MM. Fifty-four of 212 patients (25.5%) had a negative CSS and a positive WBCT for osteolytic lesions (P<0.0001). Of 66 patients with SMM based on CSS, 12 (22.2%) had osteolytic lesions on WBCT...
August 25, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28806822/-multiple-myeloma-current-status-in-diagnostic-testing-and-therapy
#13
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...
October 2017: Zeitschrift Für Orthopädie und Unfallchirurgie
https://www.readbyqxmd.com/read/28792255/host-related-immunodeficiency-in-the-development-of-multiple-myeloma
#14
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
#15
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...
October 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28709797/smoldering-multiple-myeloma-who-and-when-to-treat
#16
REVIEW
María-Victoria Mateos, Verónica González-Calle
Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder characterized by the presence of ≥ 3 g/dL serum M-protein and/or 10% to 60% bone marrow plasma cell infiltration with no myeloma-defining event. The risk of progression to active multiple myeloma (MM) is not uniform, and several markers are useful for identifying patients at high risk of progression. The definition of the disease has recently been revisited and asymptomatic MMs at 80% to 90% of progression risk at 2 years are now considered to be active MM candidates for treatment...
June 23, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28693062/-the-risk-stratification-and-treatment-of-smoldering-multiple-myeloma
#17
(no author information available yet)
No abstract text is available yet for this article.
July 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/28673317/the-ubiquitin-conjugating-enzyme-ube2o-modulates-c-maf-stability-and-induces-myeloma-cell-apoptosis
#18
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
#19
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)...
August 2017: Obesity
https://www.readbyqxmd.com/read/28592156/diagnosis-and-management-of-smoldering-multiple-myeloma-the-razor-s-edge-between-clonality-and-cancer
#20
Eli Muchtar, Shaji K Kumar, Hila Magen, Morie A Gertz
Smoldering multiple myeloma (SMM) is a rare plasma cell disorder, and as the disease is asymptomatic, diagnosis is often incidental. SMM is characterized by increased marrow infiltration by clonal plasma cells and/or elevated serum M-protein in the absence of a myeloma-defining event (MDE). In recent years, SMM has gained increased attention owing to a broadening of the criteria for MDE, which include apart from the CRAB criteria, three additional parameters. Survival advantage may be offered by early treatment in the high-risk subset, based on a single trial...
February 2018: Leukemia & Lymphoma
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