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Madhav V Dhodapkar
All cases of multiple myeloma (MM) are preceded by precursor states termed as monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM). Genetic analyses of MGUS cells have provided evidence that it is a genetically advanced lesion wherein tumor cells carry many of the genetic changes found in MM cells. Intraclonal heterogeneity is also established early during the MGUS phase. While the genetic features of MGUS or SMM cells at baseline may predict disease risk, transition to MM involves altered growth of pre-existing clones...
October 13, 2016: Blood
E Terpos, D Christoulas, E Kastritis, T Bagratuni, M Gavriatopoulou, M Roussou, A Papatheodorou, E Eleutherakis-Papaiakovou, N Kanellias, C Liakou, I Panagiotidis, M Migkou, P Kokkoris, L A Moulopoulos, M A Dimopoulos
Periostin is an extracellular matrix protein that is implicated in the biology of normal bone remodeling and in different cancer cell growth and metastasis. However, there is no information on the role of periostin in multiple myeloma (MM). Thus, we evaluated periostin in six myeloma cell lines in vitro; in the bone marrow plasma and serum of 105 newly diagnosed symptomatic MM (NDMM) patients and in the serum of 23 monoclonal gammopathy of undetermined significance (MGUS), 33 smoldering MM (SMM) patients, 30 patients at the plateau phase post-first-line therapy, 30 patients at first relapse and 30 healthy controls...
October 7, 2016: Blood Cancer Journal
Ben Boursi, Ronac Mamtani, Yu-Xiao Yang, Brendan M Weiss
No abstract text is available yet for this article.
October 5, 2016: Leukemia & Lymphoma
Alfredo Gagliardi, Claudio Carbone, Angela Russo, Rosanna Cuccurullo, Anna Lucania, Paola Della Cioppa, Gabriella Misso, Michele Caraglia, Catello Tommasino, Lucia Mastrullo
Monoclonal gammopathies are characterized by serum monoclonal component (MC) plus an intact immunoglobulin and a free light chain (FLC), or a combination of both. The measurement of FLC with Freelite(®) is the standard practice recommended by International Myeloma Working Group guidelines. Recently, Hevylite(®) heavy/light chains (HLC) assays were introduced to specifically target junctional epitopes between the heavy and light chains of intact immunoglobulins, allowing the independent quantification of the involved (MC) and uninvolved (polyclonal immunoglobulin background) HLC isotype...
October 2016: Oncology Letters
Domenico Ribatti, Angelo Vacca
Multiple myeloma (MM) mainly progresses in bone marrow (BM). Therefore, signals from the BM microenvironment are thought to play a critical role in maintaining plasma cell growth, migration, and survival. Reciprocal positive and negative interactions between plasma cells and microenvironmental cells, including endothelial cells (ECs) and fibroblasts may occur. The BM neovascularization is a constant hallmark of MM, and goes hand in hand with progression to leukemic phase. Microenvironmental factors induce MMECs and fibroblasts to become functionally different from monoclonal gammopathy of undetermined significance (MGUS) ECs (MGECs), i...
2016: Cancer Treatment and Research
María-Victoria Mateos, Ola Landgren
Monoclonal gammopathy of undetermined significance (MHUS) is characterized by the presence of a serum M-protein less than 3 g/dL, less than 10 % clonal plasma cells in the bone marrow, and the absence of myeloma-defining event. Smoldering multiple myeloma (SMM) is an asymptomatic disorder characterized by the presence of ≥3 g/dL serum M-protein and/or 10-60 % bone marrow plasma cell infiltration with no myeloma-defining event. The risk of progression to multiple myeloma (MM) requiring therapy varies greatly for individual patients, but it is uniform and 1 % per year for MGUS, while higher (10 % per year) and not uniform for SMM patients...
2016: Cancer Treatment and Research
John Gubatan, Xiaohui Wang, Abner Louissaint, Anuj Mahindra, John Vanderpool
BACKGROUND: Bone marrow sarcoidosis is extremely rare. The association between sarcoidosis and lymphoproliferative disorders has been previously speculated, although the diagnosis of sarcoidosis often precedes any hematological derangements. CASE PRESENTATION: Here, we report for the first time, a case of a 57-year-old Caucasian woman with a previous diagnosis of monoclonal gammopathy of undetermined significance (MGUS) developing hypercalcemia and renal failure with workup notable for isolated bone marrow sarcoidosis and not multiple myeloma as expected...
2016: Biomarker Research
Catarina Geraldes, Ana Cristina Gonçalves, Emília Cortesão, Marta Isabel Pereira, Adriana Roque, Artur Paiva, Letícia Ribeiro, José Manuel Nascimento-Costa, Ana Bela Sarmento-Ribeiro
BACKGROUND: Aberrant DNA methylation is considered a crucial mechanism in the pathogenesis of monoclonal gammopathies. We aimed to investigate the contribution of hypermethylation of 4 tumor suppressor genes to the multistep process of myelomagenesis. METHODS: The methylation status of p15, p16, p53, and DAPK genes was evaluated in bone marrow samples from 94 patients at diagnosis: monoclonal gammopathy of uncertain significance (MGUS) (n = 48), smoldering multiple myeloma (SMM) (n = 8) and symptomatic multiple myeloma (MM) (n = 38), and from 8 healthy controls by methylation-specific polymerase chain reaction analysis...
August 10, 2016: Clinical Lymphoma, Myeloma & Leukemia
Jayant Gite, Rohit Shrivastav, Nikhil Bhasin, Puneet Mashru, Manish Itolikar, Milind Y Nadkar
Hirata disease is a rare disease characterised by recurrent episodes of hypoglycaemia due to anti-insulin antibody. In most of these cases causative agents were sulfhydryl containing compounds like Penicillamine, Glutathione, and Methimazole. The presentation of disease closely mimics insulinoma. We report 52 years female patient presenting with recurrent episodes of hypoglycaemia due to anti-insulin antibody. On evaluation, underlying cause of antibody was found to be monoclonal gammopathy of unknown significance (MGUS)...
October 2015: Journal of the Association of Physicians of India
Pengfei Cao, Guiyuan Li, Qian Tan, Ying Zhang, Guoping Zhang, Xiaolin Li, Yuxiang He
OBJECTIVE: To investigate several abnormal genes by the fluorescence in situ hybridization (FISH) in multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS) and reactive plasmacytosis (RP), and to increase the diagnosis and differential diagnosis levels for these common plasma diseases. 
 METHODS: The clinical manifestations, image and laboratory tests and the FISH detection were retrospectively analyzed in 61 cases of newly diagnosed MM, 20 cases of MGUS and 20 cases of RP from August, 2012 to February, 2015 in the Xiangya Hospital of Central South University...
July 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Yukio Mizuno, Madoka Mori-Yoshimura, Tomoko Okamoto, Yasushi Oya, Ichizo Nishino, Miho Murata
Sporadic late onset nemaline myopathy (SLONM) associated with monoclonal gammopathy of undetermined significance (MGUS) is an adult onset myopathy with poor clinical outcomes, requiring high-dose intravenous melphalan with autologous peripheral blood stem cell transplantation (HDM-SCT). Here we report two cases of SLONM associated with MGUS in which improvements were achieved only with immunotherapy. A 39-year-old woman had a two-year history of dropped head syndrome and progressive proximal weakness. On admission, she was able to walk with assistance and had lordosis with camptocormia...
September 29, 2016: Rinshō Shinkeigaku, Clinical Neurology
Shintaro Hayashi, Shun Nagamine, Kouki Makioka, Susumu Kusunoki, Koichi Okamoto
A 71-year-old woman with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with IgA-λ monoclonal gammopathy of undetermined significance (MGUS) showed the acute development of tetraplegia, respiratory failure, and a marked fluctuation of the blood pressure. Intravenous (IV) high-dose steroid therapy (methylprednisolone: 1 g/day × 3 days), followed by oral prednisolone (PSL) (40 mg/day), and IV immunoglobulin (IVIg, 0.4 g/kg/day × 5 days) administrations resulted in the amelioration of these symptoms...
September 29, 2016: Rinshō Shinkeigaku, Clinical Neurology
M Felldin, J Ekberg, D Polanska-Tamborek, U Hansson, M Sender, M Rizell, J Svanvik, J Mölne
Prior research on donor monoclonal gammopathy of undetermined significance (MGUS) has been inadequate regarding the risk for lymphoproliferative disease in solid organ transplantation recipients. Seven organ recipients from two different donors developed lymphoproliferative disease. The origin of the malignancy was determined by use of microsatellite analysis, and the plasma of the two donors was analyzed with the use of electrophoresis. The clinical courses of the seven recipients were followed for 36-60 months...
September 2016: American Journal of Transplantation
Fanny Pojero, Alessandra Casuccio, Caterina Giambanco, Matteo Bulati, Silvio Buffa, Francesco Di Bassiano, Francesco Gervasi, Calogero Caruso, Giuseppina Colonna Romano
BACKGROUND/AIMS: Multiple myeloma (MM) is caused by proliferation of clonal plasma cells (cPCs) in bone marrow (BM), associated with numerical and functional defects in immune subsets. An impairment of B cell compartment is involved in onset/progression of the disease. METHODS: By flow cytometry, we studied distribution of naïve/transitional (IgD(+)CD27(-)), memory unswitched (IgD(+)CD27(+)), memory switched (IgD(-)CD27(+)) and double negative (DN) (IgD(-)CD27(-)) B lymphocytes in BM of control subjects, and responding and relapsing patients...
October 2016: Leukemia Research
Jorge J Castillo, Morie A Gertz
In recent years, the survival of patients with plasma cell dyscrasias has improved due to improvements in anticancer and supportive therapy. However, the risk of secondary malignancies has increased, thought to be due to a combination of environmental and disease-related factors, as well as treatment. In the present review, we evaluate the risk of secondary malignancies in patients with monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and Waldenström macroglobulinemia (WM). Patients with MGUS appear to have a higher risk of developing myeloid malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML)...
August 22, 2016: Leukemia & Lymphoma
Petra Schneiderova, Tomas Pika, Petr Gajdos, Regina Fillerova, Pavel Kromer, Milos Kudelka, Jiri Minarik, Tomas Papajik, Vlastimil Scudla, Eva Kriegova
Serum protein fingerprints associated with MGUS and MM and their changes in MM after autologous stem cell transplantation (MM-ASCT, day 100) remain unexplored. Using highly-sensitive Proximity Extension ImmunoAssay on 92 cancer biomarkers (Proseek Multiplex, Olink), enhanced serum levels of Adrenomedullin (ADM, Pcorr= .0004), Growth differentiation factor 15 (GDF15, Pcorr= .003), and soluble Major histocompatibility complex class I-related chain A (sMICA, Pcorr= .023), all prosurvival and chemoprotective factors for myeloma cells, were detected in MM comparing to MGUS...
August 12, 2016: Oncotarget
P A von dem Borne, M F Jonkman, R van Doorn
Subcorneal pustular dermatosis (SPD) or Sneddon-Wilkinson disease is a rare pustular skin disease that follows a chronic relapsing course. A well-known association exists between SPD and IgA monoclonal gammopathy of undetermined significance (IgA MGUS), which exists in up to 40% of cases. SPD has also been observed in IgA myeloma patients. In SPD direct and indirect immunofluorescence studies do not reveal in vivo bound IgA to the epithelial cell surface, in contrast to IgA pemphigus that has similar clinico-pathological features...
August 12, 2016: British Journal of Dermatology
Satoru Kosugi, Hirohiko Shibayama, Eiji Nakatani, Toru Kida, Kensuke Ohta, Hidemi Kaneko, Hideo Yagi, Hirokazu Tanaka, Shin-Ichi Fuchida, Aya Nakaya, Masayuki Kobayashi, Junya Kuroda, Yuri Kamitsuji, Nobuhiko Uoshima, Yoko Adachi, Mitsuru Tsudo, Chihiro Shimazaki, Shosaku Nomura, Masayuki Hino, Itaru Matsumura, Masashi Taniwaki, Yuzuru Kanakura, Akifumi Takaori-Kondo
The incidence of second primary malignancies (SPMs) in Japanese patients with myeloma or myeloma-related diseases was studied by using the Kansai Myeloma Forum (KMF) database registered from November 2012 to March 2015. We studied 1,571 cases. Hematologic malignancies were documented in 10 patients, and solid tumors in 36 during this period. The cumulative 5-year incidence was estimated to be 1.0% for hematological malignancies and 3.7% for solid tumors. In the patients with smoldering myeloma or MGUS without treatment, solid tumors but not hematologic malignancies developed, though the cumulative incidence of each malignancy did not differ significantly from that in patients receiving treatment...
July 2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Giovanni D'Arena, Giovanni Rossi, Luca Laurenti, Teodora Statuto, Fiorella D'Auria, Luciana Valvano, Vittorio Simeon, Aldo Giudice, Idanna Innocenti, Vincenzo De Feo, Rosanna Filosa, Pellegrino Musto
The frequency and function of regulatory T-cells (Tregs) in multiple myeloma (MM) are still matter of debate. The percentage and absolute number of circulating Tregs (CD4(+)CD25(+high  density)CD127(-/low  density)) from 39 patients with untreated MM and 44 patients with monoclonal gammopathies of uncertain significance (MGUS) were tested and compared with 20 healthy subjects as controls. The mean percentage number of circulating Tregs was 2.1%  ± 1.0 (range 0.75-6.1%) in MM patients; 2.1%  ± 0...
2016: Journal of Immunology Research
Mohamed-Amine Hamouda, Arnaud Jacquel, Guillaume Robert, Alexandre Puissant, Valentine Richez, Romeo Cassel, Nina Fenouille, Sandrine Roulland, Jerome Gilleron, Emmanuel Griessinger, Alix Dubois, Beatrice Bailly-Maitre, Diogo Goncalves, Aude Mallavialle, Pascal Colosetti, Sandrine Marchetti, Martine Amiot, Patricia Gomez-Bougie, Nathalie Rochet, Marcel Deckert, Herve Avet-Loiseau, Paul Hofman, Jean-Michel Karsenti, Pierre-Yves Jeandel, Claudine Blin-Wakkach, Bertrand Nadel, Thomas Cluzeau, Kenneth C Anderson, Jean-Gabriel Fuzibet, Patrick Auberger, Frederic Luciano
Multiple myeloma (MM) evolves from a premalignant condition known as monoclonal gammopathy of undetermined significance (MGUS). However, the factors underlying the malignant transformation of plasmocytes in MM are not fully characterized. We report here that Eµ-directed expression of the antiapoptotic Bcl-B protein in mice drives an MM phenotype that reproduces accurately the human disease. Indeed, with age, Eµ-bcl-b transgenic mice develop the characteristic features of human MM, including bone malignant plasma cell infiltration, a monoclonal immunoglobulin peak, immunoglobulin deposit in renal tubules, and highly characteristic bone lytic lesions...
August 22, 2016: Journal of Experimental Medicine
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