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Plasma cell myeloma

N Meuleman, M Vercruyssen
Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant plasma cell disorder. MGUS is a common disorder and the diagnosis is often made accidentally when a protein electrophoresis is performed in a routine blood test or during a biological assessment for other conditions. In the absence of biological abnormalities or clinical symptoms suggesting a plasma or lymphoplasma-cell disorder, there is no indication for routine screening of the monoclonal protein. When MGUS is diagnosed, the risk of transformation into myeloma or other lymphoproliferative disorders is estimated at 1 % per year...
2018: Revue Médicale de Bruxelles
Julia Paton-Hough, Simon Tazzyman, Holly Evans, Darren Lath, Jenny M Down, Alanna C Green, John A Snowden, Andrew D Chantry, Michelle A Lawson
Multiple myeloma is a plasma cell malignancy, which develops in the bone marrow and frequently leads to severe bone destruction. Current antiresorptive therapies to treat the bone disease do little to repair damaged bone; therefore, new treatment strategies incorporating bone anabolic therapies are urgently required. We hypothesized that combination therapy using the standard of care antiresorptive zoledronic acid (Zol) with a bone anabolic (anti-TGFβ/1D11) would be more effective at treating myeloma-induced bone disease than Zol therapy alone...
October 15, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Linlin Zhang, Ya Xu, Li Wang, Hong Liu
Receptor for activated C kinase 1 (RACK1), a scaffold protein, plays a crucial role in the progression of various cancers. However, the biological function and underlying mechanism of RACK1 in multiple myeloma (MM) cells remain unclear. The present study aimed to explore the function of RACK1 on the cell proliferation, adhesion, and bortezomib-induced apoptosis in MM. We found that RACK1 was significantly overexpressed in myeloma cell lines and primary myeloma cells compared with normal bone marrow plasma cells...
October 10, 2018: International Journal of Biological Macromolecules
Christina Eberhardt, Alexandra Malbon, Barbara Riond, Angelika Schoster
CASE DESCRIPTION A 27-year-old Dutch Warmblood mare was evaluated because of a history of lethargy, reluctance to move, weight loss, persistent hyperproteinemia, and recurrent episodes of mild lameness. CLINICAL FINDINGS Hematologic evaluation revealed anemia (RBC concentration, 3.84 × 106 cells/μL), thrombocytopenia (47 × 103 thrombocytes/μL), and hyperproteinemia (total protein concentration, 11.2 g/dL) with hyperglobulinemia and hypoalbuminemia. Results of protein electrophoresis of serum and urine samples indicated a monoclonal gammopathy; the paraprotein was identified as a κ light chain...
November 1, 2018: Journal of the American Veterinary Medical Association
Patricia Gomez-Bougie, Sophie Maiga, Benoît Tessoulin, Jessie Bourcier, Antoine Bonnet, Manuel S Rodriguez, Steven Le Gouill, Cyrille Touzeau, Philippe Moreau, Catherine Pellat-Deceunynck, Martine Amiot
BH3-mimetics are promising drugs for hematologic malignancies that trigger cell death by promoting the release of pro-apoptotic BCL2 family members from anti-apoptotic proteins. Multiple myeloma is considered to be a disease dependent mainly on MCL1 for survival based mostly on studies using cell lines. We used a BH3-mimetic toolkit to study the dependency on BCL2, BCLXL or MCL1 in malignant plasma cells from 60 patients. Dependencies were analyzed using an unbiased BH3-mimetics cell-death clustering by k-means...
October 11, 2018: Blood
Roula Katerji, Chad A Hudson
The combination of polycythemia and plasma cell myeloma occurring concurrently is very rare and few cases have been reported in the literature. Further, the vast majority of these cases are cases of polycythemia vera and myeloma. Here, we present a case of polycythemia of undetermined etiology and myeloma. The patient is a 48-year-old Caucasian male who was originally diagnosed with polycythemia of undetermined etiology. Twelve years later, when a bone marrow biopsy was performed in an attempt to determine the etiology of the polycythemia, findings diagnostic of plasma cell myeloma were discovered...
2018: Case Reports in Pathology
Masaki Ri
Multiple myeloma (MM) is a mature plasma cell neoplasm characterized by the excessive production of monoclonal antibodies and various cytokines. Therefore, MM cells are highly dependent on the ubiquitin-proteasome pathway and the well-differentiated unfolded protein response in the endoplasmic reticulum. Bortezomib, the first approved proteasome inhibitor (PI) for the treatment of MM, is widely used as a therapeutic agent for patients with MM, including newly diagnosed and relapsed/refractory (RR) cases. However, severe peripheral neuropathy and gastrointestinal disorders often occur during bortezomib treatment, which leads to inadequate treatment of MM owing to the interruption or reduction in bortezomib administration...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Zsuzsanna Kovacs, Andras Guttman
Multiple myeloma (MM) is characterized as the clonal proliferation of malignant plasma B-lymphocytes and even as of today, it is an incurable disease. MM accounts for approximately 10% of all hematologic cancers. Its molecular pathogenesis is poorly understood, but the bone marrow microenvironment of tumor cells and genetic factors have apparent roles in the process. Accurate diagnosis is important to properly identify and stratify the disease, however, MM identification steps are time-consuming and expensive...
October 8, 2018: Current Molecular Medicine
Ravi K Anchoori, Rosie Jiang, Shiwen Peng, Ruey-Shyang Soong, Aliyah Algethami, Michelle A Rudek, Nicole Anders, Chien-Fu Hung, Xiang Chen, Xiuxiu Lu, Olumide Kayode, Marzena Dyba, Kylie J Walters, Richard B S Roden
Substitution of the m , p -chloro groups of bis-benzylidinepiperidone RA190 for p -nitro, generating RA183, enhanced covalent drug binding to Cys88 of RPN13. Treatment of cancer cell lines with RA183 inhibited ubiquitin-mediated protein degradation, resulting in rapid accumulation of high-molecular-weight polyubiquitinated proteins, blockade of NFκB signaling, endoplasmic reticulum stress, an unfolded protein response, production of reactive oxygen species, and apoptotic cell death. High-grade ovarian cancer, triple-negative breast cancer, and multiple myeloma cell lines were particularly vulnerable to RA183...
September 30, 2018: ACS Omega
Lien De Beck, Sarah Melhaoui, Kim De Veirman, Eline Menu, Elke De Bruyne, Karin Vanderkerken, Karine Breckpot, Ken Maes
Immune evasion is an important driver of disease progression in the plasma cell malignancy multiple myeloma. Recent work highlights the potential of epigenetic modulating agents as tool to enhance anti-tumor immunity. The immune modulating effects of the combination of a DNA methyltransferase inhibitor and a histone deacetylase inhibitor in multiple myeloma is insufficiently characterized. Therefore, we used the murine immunocompetent 5T33MM model to investigate hallmarks of immunogenic cell death as well as alterations in the immune cell constitution in the bone marrow of diseased mice in response to the DNA methyltransferase inhibitor decitabine and the histone deacetylase inhibitor quisinostat...
2018: Oncoimmunology
Lia A Moulopoulos, Vassilis Koutoulidis, Jens Hillengass, Elena Zamagni, Jesus D Aquerreta, Charles L Roche, Suzanne Lentzsch, Philippe Moreau, Michele Cavo, Jesus San Miguel, Meletios A Dimopoulos, S Vincent Rajkumar, Brian G M Durie, Evangelos Terpos, Stefan Delorme
Whole Body Low Dose CT (WBLDCT) has important advantages as a first-line imaging modality for bone disease assessment in patients with plasma cell disorders and has been included in the 2014 International Myeloma Working Group (IMWG) criteria for multiple myeloma (MM) definition. Nevertheless, standardization guidelines for the optimal use of WBLDCT in MM patients are still lacking, preventing its more widespread use, both in daily practice and clinical trials. The aim of this report by the Bone Group of the IMWG is to provide practical recommendations for the acquisition, interpretation and reporting of WBLDCT in patients with multiple myeloma and other plasma cell disorders...
October 4, 2018: Blood Cancer Journal
Xavier Leleu, Thomas G Martin, Hermann Einsele, Roger M Lyons, Brian G M Durie, Karim S Iskander, Sikander Ailawadhi
Proteasome inhibition is an established treatment strategy for patients with multiple myeloma as proteasome inhibitors (PIs) selectively target and disrupt the protein metabolism of aberrant plasma cells. Since the introduction of the first-in-class PIs bortezomib, the therapeutic landscape for multiple myeloma has shifted with the development of next-generation PIs (carfilzomib and ixazomib) and new classes of agents. Treatment with modern combination therapies has been shown to result in deep responses and improved outcomes, and these potent regimens are increasingly used as frontline therapy...
September 5, 2018: Clinical Lymphoma, Myeloma & Leukemia
Laurie Herviou, Alboukadel Kassambara, Stéphanie Boireau, Nicolas Robert, Guilhem Requirand, Carsten Müller-Tidow, Laure Vincent, Anja Seckinger, Hartmut Goldschmidt, Guillaume Cartron, Dirk Hose, Giacomo Cavalli, Jerome Moreaux
BACKGROUND: Multiple myeloma (MM) is a malignant plasma cell disease with a poor survival, characterized by the accumulation of myeloma cells (MMCs) within the bone marrow. Epigenetic modifications in MM are associated not only with cancer development and progression, but also with drug resistance. METHODS: We identified a significant upregulation of the polycomb repressive complex 2 (PRC2) core genes in MM cells in association with proliferation. We used EPZ-6438, a specific small molecule inhibitor of EZH2 methyltransferase activity, to evaluate its effects on MM cells phenotype and gene expression prolile...
October 3, 2018: Clinical Epigenetics
Mu Hao, Bart Barlogie, Guido Tricot, Lanting Liu, Luqui Qiu, John D Shaughnessy, Fenghuang Zhan
PURPOSE: That the malignant clone of Waldenström's macroglobulinemia (WM) demonstrates significant intraclonal heterogeneity with respect to plasmacytoid differentiation indicates the mechanistic complexity of tumorigenesis and progression. Identification of WM genes by comparing different stages of B cells may provide novel druggable targets. EXPERIMENTAL DESIGN: The gene expression signatures of CD19+ B cells (BC) and CD138+ plasma cells (PC) from 19 patients with WM were compared to those of BC from peripheral blood and tonsil and to those of PC from the marrow of healthy (N-PC) and multiple myeloma donors (MM-PC), as well as tonsil (T-PC)...
October 2, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Tomoki Suichi, Sonoko Misawa, Yasunori Sato, Minako Beppu, Emiko Sakaida, Yukari Sekiguchi, Kazumoto Shibuya, Keisuke Watanabe, Hiroshi Amino, Satoshi Kuwabara
OBJECTIVE: To propose the optimal diagnostic criteria for polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome using appropriate statistical methods and disease controls. METHODS: This retrospective cohort study included 104 consecutive patients with suspected POEMS syndrome, among whom a gold standard group of 60 patients with definitive POEMS syndrome diagnosis were followed for at least 12 months to strictly exclude other disorders mimicking POEMS syndrome and to confirm response to POEMS syndrome-specific treatment...
October 2, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
Antonio G Solimando, Azzurra Sportelli, Teresa Troiano, Lucia Demarinis, Francesca Di Serio, Angelo Ostuni, Franco Dammacco, Angelo Vacca, Roberto Ria
RATIONALE: Type I cryoglobulinemia is a rare and life-threatening condition. It occurs mainly in B-cell lymphoproliferative disorder. In almost half of the patients, type I cryoglobulinemia is characterized by severe cutaneous involvement. PATIENT CONCERNS: A 71-year-old man comes to our observation because of the onset of persistence of paresthesia and painful acrocyanosis in the fingers and toes. IgG-k multiple myeloma treated with chemotherapy and radiation therapy on the left iliac wing characterized his clinical history...
September 2018: Medicine (Baltimore)
Wenzhen Yang, Jing Zheng, Ruihao Li, Haijun Ren, Boru Hou, Zhiyong Zhao, Dengfeng Wang, Gang Wang, Jixing Liu, Guizhong Yan, Dong Wang, Xinding Zhang
RATIONALE: MM is a malignant tumor originating from the plasma cells of the bone marrow. Central nervous system myelomatosis is very rare and may be a complication of MM. PATIENT CONCERNS: A 60-year-old man presented with a slowly growing soft mass at his right frontal scalp after a mild head injury 6 months ago. DIAGNOSES: Neuroradiological examinations revealed a solid intracranial-extracranial mass with an osteolytic lesion in the skull...
September 2018: Medicine (Baltimore)
Tianhua Yu, Zhihua Xu, Xuanhe Zhang, Lan Men, Haiying Nie
Long intergenic non‑protein coding RNA 152 (LINC00152, also known as cytoskeleton regulator RNA) is reportedly involved in the development and progression of various types of human malignancy. However, the functional role of LINC00152 in multiple myeloma (MM) and the underlying molecular mechanisms have remained elusive. The present study aimed to investigate the role of LINC00152 in the genesis of MM and the potential molecular mechanisms. It was identified that the expression of LINC00152 was significantly upregulated in plasma cells from patients with MM vs...
September 21, 2018: Oncology Reports
Evgeniya A Angelova, Shaoying Li, Wei Wang, Carlos Bueso-Ramos, Guilin Tang, L Jeffrey Medeiros, Pei Lin
IgM plasma cell myeloma (PCM) is a rare subtype of myeloma and its response to novel therapies has not been fully characterized. We describe clinicopathological features and outcome of 17 patients with IgM PCM (11 men and 6 women) with a median age of 63years. Patients presented with serum hyperviscosity (77%), bone lesions (71%), anemia (65%), renal dysfunction (53%), and hypercalcemia (35%). Median serum IgM level was 6.4g/dL (0.7-12.1g/dL). Bone marrow plasma cells (median 80%, range 20-90%) were frequently of lymphoplasmacytic type (8/17, 47%)...
September 25, 2018: Human Pathology
Michelle Le, Balarama Krishna Surapaneni, Vardhmaan Jain, Rakesh Vinayek, Sudhir K Dutta
Extramedullary plasmacytomas (EMP) are a subcategory of plasma cell neoplasm that involves organs outside the bone marrow. Involvement of the pancreas is relatively rare, reported in only 2.3% of autopsies. Radiologic findings in plasmacytoma are nonspecific, but endoscopic ultrasound fine-needle aspiration is a fast and reliable technique to acquire a histologic sample for initial diagnosis. Recently, the use of fluorine-18 fluorodeoxyglucose PET/CT has been recommended in patients with active multiple myeloma and solitary plasmacytoma...
2018: Clinical Medicine Insights. Gastroenterology
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