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https://www.readbyqxmd.com/read/27910020/cytoplasmic-immunoglobulin-light-chain-revelation-and-interphase-fluorescence-in-situ-hybridization-in-myeloma
#1
Sarah Moore, Jeffrey M Suttle, Mario Nicola
The cytogenetic analysis of plasma cell myeloma (PCM) allows stratification of patients so that prognosis may be determined and appropriate therapeutic options can be discussed. Owing to the patchy nature of the disease in the bone marrow (BM), the low proliferative activity of plasma cells and the cryptic nature of some PCM-associated cytogenetic changes, karyotypic analysis in this disease should be augmented with targeted interphase fluorescence in situ hybridization (FISH). Immunofluorescent revelation of cytoplasmic immunoglobulin light chains, together with interphase FISH (cIg-FISH), allows the identification of plasma cells within a sample so that they may be scored preferentially...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27909306/rpl5-on-1p22-1-is-recurrently-deleted-in-multiple-myeloma-and-its-expression-is-linked-to-bortezomib-response
#2
I J F Hofman, M Van Duin, E De Bruyne, L Fancello, G Mulligan, E Geerdens, E Garelli, C Mancini, H Lemmens, M Delforge, P Vandenberghe, I Wlodarska, A Aspesi, L Michaux, K Vanderkerken, P Sonneveld, K De Keersmaecker
Chromosomal region 1p22 is deleted in ⩾20% of multiple myeloma (MM) patients, suggesting the presence of an unidentified tumor suppressor. Using high-resolution genomic profiling, we delimit a 58 kb minimal deleted region (MDR) on 1p22.1 encompassing two genes: ectopic viral integration site 5 (EVI5) and ribosomal protein L5 (RPL5). Low mRNA expression of EVI5 and RPL5 was associated with worse survival in diagnostic cases. Patients with 1p22 deletion had lower mRNA expression of EVI5 and RPL5, however, 1p22 deletion status is a bad predictor of RPL5 expression in some cases, suggesting that other mechanisms downregulate RPL5 expression...
December 2, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27909220/role-of-serum-free-light-chain-assay-in-the-detection-of-early-relapse-and-prediction-of-prognosis-after-relapse-in-multiple-myeloma-patients-treated-upfront-with-novel-agents
#3
Paola Tacchetti, Annalisa Pezzi, Elena Zamagni, Lucia Pantani, Serena Rocchi, Beatrice Anna Zannetti, Katia Mancuso, Ilaria Rizzello, Michele Cavo
No abstract text is available yet for this article.
December 1, 2016: Haematologica
https://www.readbyqxmd.com/read/27904737/a-clinical-update-on-the-role-of-carfilzomib-in-the-treatment-of-relapsed-or-refractory-multiple-myeloma
#4
REVIEW
B Franken, N W C J van de Donk, J C Cloos, S Zweegman, H M Lokhorst
Even though the prognosis of patients with multiple myeloma is continuing to improve, all patients eventually develop relapsed refractory disease. Several novel therapeutics have been developed in the last few years including the second-generation proteasome inhibitor carfilzomib which has been approved for patients with relapsed and refractory multiple myeloma in the United States since 2012. Recently data from several phase III studies have become available showing the promising efficacy of carfilzomib in combination with lenalidomide, which led to the renewed approval of carfilzomib in combination with lenalidomide and dexamethasone for relapsed myeloma in 2015...
December 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27903915/max-is-an-epigenetic-sensor-of-5-carboxylcytosine-and-is-altered-in-multiple-myeloma
#5
Dongxue Wang, Hideharu Hashimoto, Xing Zhang, Benjamin G Barwick, Sagar Lonial, Lawrence H Boise, Paula M Vertino, Xiaodong Cheng
The oncogenic transcription factor MYC and its binding partner MAX regulate gene expression by binding to DNA at enhancer-box (E-box) elements 5'-CACGTG-3'. In mammalian genomes, the central E-box CpG has the potential to be methylated at the 5-position of cytosine (5mC), or to undergo further oxidation to the 5-hydroxymethyl (5hmC), 5-formyl (5fC), or 5-carboxyl (5caC) forms. We find that MAX exhibits the greatest affinity for a 5caC or unmodified C-containing E-box, and much reduced affinities for the corresponding 5mC, 5hmC or 5fC forms...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27903157/obesity-and-other-cancers
#6
Lin Yang, Bettina F Drake, Graham A Colditz
Purpose Evidence on overweight, obesity, and an increased risk of cancer continues to accumulate and was updated in the 2016 handbook on weight control from the International Agency for Research on Cancer (IARC). The underlying primary data, together with dose-response meta-analysis and, finally, pooled analysis of individual participant data, add insight into the relation between obesity and cancer risk and prognosis. We summarize the evidence for mortality from prostate cancer, hematologic malignancies, and kidney cancer...
December 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27894203/management-of-adverse-events-induced-by-next-generation-immunomodulatory-drug-and-proteasome-inhibitors-in-multiple-myeloma
#7
Marco Salvini, Francesca Bonello, Mario Boccadoro, Alessandra Larocca
In the last decade the introduction of novel agents has strongly improved multiple myeloma prognosis by doubling median overall survival. Unfortunately disease relapse is very common and patients may become refractory to previous drugs. Therefore, new therapeutic strategies are urgently needed. Areas covered. We have reviewed the available data on next generation novel agents, particularly immunomodulatory drug pomalidomide and proteasome inhibitors carfilzomib and ixazomib, the latter being the first-in-class orally available...
November 29, 2016: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/27893836/prognostic-value-of-serum-free-light-chains-measurements-in-multiple-myeloma-patients
#8
José Luis García de Veas Silva, Carmen Bermudo Guitarte, Paloma Menéndez Valladares, Johanna Carolina Rojas Noboa, Krysta Kestler, Rafael Duro Millán
BACKGROUND: The outcome for patients with Multiple Myeloma (MM) is highly variable, therefore, the existence of robust and easy to determine prognostic markers is extremely important for an efficient management of these patients. Presently, there is a debate about the role of the serum free light chains (sFLC) in the prognosis of MM patients both at diagnosis and after treatment. The aim of this study is to evaluate in a cohort of newly diagnosed MM patients from the Southern area of Spain, the prognostic value of sFLC both at baseline and after treatment...
2016: PloS One
https://www.readbyqxmd.com/read/27892767/epigenetic-modifications-in-multiple-myeloma-recent-advances-on-the-role-of-dna-and-histone-methylation
#9
Nicola Amodio, Patrizia D'Aquila, Giuseppe Passarino, Pierfrancesco Tassone, Dina Bellizzi
Multiple Myeloma (MM) is a clonal late B-cell disorder accounting for about 13% of hematological cancers and 1% of all neoplastic diseases. Recent studies on the molecular pathogenesis and biology of MM have highlighted a complex epigenomic landscape contributing to MM onset, prognosis and high individual variability. Areas covered: We describe here the current knowledge on epigenetic events characterizing MM initiation and progression, focusing on the role of DNA and histone methylation and on the most promising epi-therapeutic approaches targeting the methylation pathway...
November 28, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27870103/role-of-immunotherapy-in-targeting-the-bone-marrow-microenvironment-in-multiple-myeloma-an-evolving-therapeutic-strategy
#10
Clement Chung
Multiple myeloma (referred to henceforth as myeloma) is a B-cell malignancy characterized by unregulated growth of plasma cells in the bone marrow. The treatment paradigm for myeloma underwent significant evolution in the last decade, with an improved understanding of the pathogenesis of the disease as well as the development of therapeutic agents that target not only the tumor cells but also their microenvironment. Despite these therapeutic advances, the prognosis of patients with relapsed or refractory myeloma remains poor...
November 21, 2016: Pharmacotherapy
https://www.readbyqxmd.com/read/27868410/-expression-of-microrna-221-222-in-patients-with-monoclonal-gammopathy-of-undetermined-significance-and-multiple-myeloma
#11
Suwen Yang, Wei Wang, Hong Jin, Yuhong Zhong, Xinyou Xie
Objective: To detect the expression of miR-221/222 in serum and plasma cells in patients with monoclonal gammopathy of undetermined significance(MGUS) and multiple myeloma(MM), and to explore the possibility of miR-221/222 as biomarkers in the diagnosis and prognosis predicting of MGUS and MM. Methods: Bone marrow and serum samples from 14 patients with newly diagnosed MGUS, 81 patients with newly diagnosed or relapsed MM and 10 controls were collected from Sir Run Run Shaw Hospital of Zhejiang University and Tongde Hospital of Zhejiang Province during January 2013 and December 2015...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/27857131/epigenetic-silencing-of-mir-137-induces-drug-resistance-and-chromosomal-instability-by-targeting-aurka-in-multiple-myeloma
#12
Y Qin, S Zhang, S Deng, G An, X Qin, F Li, Y Xu, M Hao, Y Yang, W Zhou, H Chang, L Qiu
Multiple myeloma (MM) is the second most prevalent hematologic malignancy. Aberrant microRNAs (miRNAs) expression has been shown to be involved in the pathogenesis of MM. In this study, we further demonstrated that miR-137 was significantly downregulated in MM and negatively correlated with clinical prognosis. Moreover, we described the epigenetic regulation of miR-137 and its association with progression free survival in MM patients. Furthermore, overexpression of miR-137 in MM cell line (miR-137OE) increased its sensitivity to bortezomib and eprirubicin in vitro...
November 18, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27852046/elevated-neutrophil-to-lymphocyte-ratio-and-monocyte-to-lymphocyte-ratio-and-decreased-platelet-to-lymphocyte-ratio-are-associated-with-poor-prognosis-in-multiple-myeloma
#13
Lihui Shi, Xiaoqi Qin, Huijun Wang, Yonghui Xia, Yuanyuan Li, Xuejing Chen, Lei Shang, Yu-Tzu Tai, Xiaoyan Feng, Prakrati Acharya, Chirag Acharya, Yan Xu, Shuhui Deng, Mu Hao, Dehui Zou, Yaozhong Zhao, Kun Ru, Lugui Qiu, Gang An
Elevated inflammatory markers are associated with poor outcomes in various types of cancers; however, their clinical significance in multiple myeloma (MM) have seldom been explored. This study investigated the prognostic relevance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) in MM. Totally 559 MM patients were included in this study. NLR, PLR and MLR were calculated from whole blood counts prior to therapy. Kaplan-Meier curves and multivariate Cox proportional models were used for the evaluation of the survival...
November 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27833099/proteomic-characterization-of-the-world-trade-center-dust-activated-mdig-and-c-myc-signaling-circuit-linked-to-multiple-myeloma
#14
Kai Wu, Lingzhi Li, Chitra Thakur, Yongju Lu, Xiangmin Zhang, Zhengping Yi, Fei Chen
Several epidemiological studies suggested an increased incidence rate of multiple myeloma (MM) among first responders and other individuals who exposed to World Trade Center (WTC) dust. In this report, we provided evidence showing that WTC dust is potent in inducing mdig protein and/or mRNA in bronchial epithelial cells, B cells and MM cell lines. An increased mdig expression in MM bone marrow was observed, which is associated with the disease progression and prognosis of the MM patients. Through integrative genomics and proteomics approaches, we further demonstrated that mdig directly interacts with c-myc and JAK1 in MM cell lines, which contributes to hyperactivation of the IL-6-JAK-STAT3 signaling important for the pathogenesis of MM...
November 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27812251/comparative-evaluation-of-common-comorbidity-scores-and-freiburger-comorbidity-index-as-prognostic-variables-in-a-real-life-multiple-myeloma-population
#15
Birgul Onec, Harika Okutan, Murat Albayrak, Esra Sarıbacak Can, Vedat Aslan, Ozge Soyer Kosemehmetoglu, Basak Unver Koluman
Multiple myeloma (MM) is a disease of the geriatric population with a median age at diagnosis of 69 years but most clinicians consider performance status and comorbidities rather than chronological age in determining prognosis and treatment. The purpose of this study was to assess whether and which comorbidity indices predict survival in a real life population of MM. We calculated Charlson Comorbidity Index (CCI), age combined Charlson index (CCI-age), Hematopoietic cell transplantation-specific comorbidity index (HCT-SCI) and Freiburger comorbidity index (FCI) retrospectively for 66 MM patients and compared their impact on treatment responses and overall survival (OS)...
December 2016: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/27807282/genetic-interrogation-of-circulating-multiple-myeloma-cells-at-single-cell-resolution
#16
Jens G Lohr, Sora Kim, Joshua Gould, Birgit Knoechel, Yotam Drier, Matthew J Cotton, Daniel Gray, Nicole Birrer, Bang Wong, Gavin Ha, Cheng-Zhong Zhang, Guangwu Guo, Matthew Meyerson, Andrew J Yee, Jesse S Boehm, Noopur Raje, Todd R Golub
Multiple myeloma (MM) remains an incurable disease, with a treatment-refractory state eventually developing in all patients. Constant clonal evolution and genetic heterogeneity of MM are a likely explanation for the emergence of drug-resistant disease. Monitoring of MM genomic evolution on therapy by serial bone marrow biopsy is unfortunately impractical because it involves an invasive and painful procedure. We describe how noninvasive and highly sensitive isolation and characterization of circulating tumor cells (CTCs) from peripheral blood at single-cell resolution recapitulate MM in the bone marrow...
November 2, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27795764/-primary-plasma-cell-leukemia-about-3-cases
#17
Mouhcine Miloudi, Nezha Messaoudi
Plasma cell leukemia is a rare hematologic malignancy defined by the presence of more than 20% of leukocyte count plasma cells or by a number of circulating plasma cells greater than 2 × 10(9)/L (2G/L). It may be primary in 60% of cases and it manifests itself immediately as a leukemia or as a secondary event, in 40% of cases, complicating a previously diagnosed multiple myeloma. Given the rarity of this condition, only a few cases have been reported in the literature. It is characterized by its aggressiveness and poor prognosis...
2016: Pan African Medical Journal
https://www.readbyqxmd.com/read/27795224/the-effect-of-the-suppressed-levels-of-uninvolved-immunoglobulins-on-the-prognosis-of-symptomatic-multiple-myeloma
#18
Murat Sarı, Selma Sarı, Meliha Nalcacı
OBJECTIVE: The majority of MM patients have high levels of monoclonal immunoglobulin in the serum and/or urine and suppressed levels of the uninvolved immunoglobulins [1]. The prognostic significance of this phenomenon has not been assessed sufficiently. In this study, our aim is to evaluate the prognostic significance of uninvolved immunoglobulin suppression measured by nephelometry in patients with new symptomatic MM and the association with other features of the disease. MATERIALS AND METHODS: Between August 2003 and February 2015, 137 patients who were referred for the treatment of new diagnosis of symptomatic myeloma to the Hematology Department polyclinics of Istanbul University Istanbul School of Medicine were prospectively included and had available pre-treatment immunoglobulin levels measured by nephelometry...
October 31, 2016: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/27793878/maf-protein-mediates-innate-resistance-to-proteasome-inhibition-therapy-in-multiple-myeloma
#19
Ya-Wei Qiang, Shiqiao Ye, Yu Chen, Amy F Buros, Ricky Edmonson, Frits Van Rhee, Bart Barlogie, Joshua Epstein, Gareth J Morgan, Faith E Davies
Multiple myeloma (MM) patients with the t(14;16) translocation have a poor prognosis, and unlike other molecular subgroups, their outcome has not improved with the introduction of bortezomib. The mechanism underlying innate resistance of MM to bortezomib is unknown. In the present study, we have investigated how MAF overexpression impacts resistance to proteasome inhibitor (PI) therapy (bortezomib and carfilzomib). High levels of MAF protein were found in t(14;16) cell lines, cell lines from the t(4;14) subgroup had intermediate levels, while cell lines from the other subgroups had low levels...
October 28, 2016: Blood
https://www.readbyqxmd.com/read/27784403/-research-progress-on-role-of-flow-cytometry-in-diagnosis-of-multiple-myeloma-review
#20
Zhi-Jun Bao, Xu Liu
Multiple myeloma (MM), the second common malignant tumor in the blood system, is a kind of B cell malignancy and its prognosis is poor. The diagnosis of MM is mainly based on the number of abnormal plasma cells and the presence of monoclonal protein in the blood or urine, but there are limitations for diagnosis of MM. Multi-parameter flow cytometry analysis is increasingly used in the in the diagnosis of MM. Therefore, this review focuses on characteristics of immunophenotypes of malignant plasma cells and myeloma progenitor cells...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
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