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Molecular myeloma

Elisa Taiana, Domenica Ronchetti, Vanessa Favasuli, Katia Todoerti, Martina Manzoni, Nicola Amodio, Pierfrancesco Tassone, Luca Agnelli, Antonino Neri
No abstract text is available yet for this article.
September 13, 2018: Haematologica
Cheryl Jacobs Smith, Stefan Ambs, Ola Landgren
Multiple myeloma is a rare plasma cell cancer, and incidence rates among patients of African descent are about twice those among patients of European descent. Rates of multiple myeloma vary among different populations, but the reasons for the racial disparities in multiple myeloma are largely unknown. Epidemiology has identified risk factors for multiple myeloma including race, advanced age, gender, family history, and exposure to different genetic toxins including radiation. Race and ancestry play a large role in predicting the risk for multiple myeloma, yet there exists a paucity of literature that explores the molecular contribution of race and ancestry to disease...
August 28, 2018: Blood Cancer Journal
Jo Caers, Laurent Garderet, K Martin Kortüm, Michael E O'Dwyer, Niels W C J van de Donk, Mascha Binder, Sandra Maria Dold, Francesca Gay, Jill Corre, Yves Beguin, Heinz Ludwig, Alessandra Larocca, Christoph Driessen, Meletios A Dimopoulos, Mario Boccadoro, Martin Gramatzki, Sonja Zweegman, Hermann Einsele, Michele Cavo, Hartmut Goldschmidt, Pieter Sonneveld, Michel Delforge, Holger W Auner, Evangelos Terpos, Monika Engelhardt
The diagnosis of multiple myeloma can be challenging, even for experienced physicians, and requires close collaboration between multiple disciplines (orthopedics, radiology, nuclear medicine, radiation therapy, hematology and oncology) before the final diagnosis of myeloma is made. The definition of multiple myeloma is based on the presence of clinical, biochemical, histo-pathological, and radiological disease markers. At presentation and during follow-up, specific tests are needed for exact disease characterization and correct diagnosis...
August 31, 2018: Haematologica
Giulia Biancon, Silvia Gimondi, Antonio Vendramin, Cristiana Carniti, Paolo Corradini
Novel treatments for multiple myeloma (MM) have increased rates of complete response, raising interest in more accurate methods to evaluate residual disease. Cell-free tumor DNA (cfDNA) analysis may represent a minimally invasive approach complementary to multiparameter flow cytometry (MFC) and molecular methods on bone marrow aspirates. A sequencing approach using the Ion Torrent Personal Genome Machine was applied to identify clonal IGH gene rearrangements in tumor plasma cells (PCs) and in serial plasma samples of 25 patients with MM receiving second-line therapy...
August 28, 2018: Journal of Molecular Diagnostics: JMD
Lucas L Bennink, Yang Li, Bumjin Kim, Ik Jae Shin, Boi Hoa San, Maurizio Zangari, Donghoon Yoon, S Michael Yu
Degradation of the extracellular matrix (ECM) is one of the fundamental factors contributing to a variety of life-threatening or disabling pathological conditions. However, a thorough understanding of the degradation mechanism and development of new ECM-targeting diagnostics are severely hindered by a lack of technologies for direct interrogation of the ECM structures at the molecular level. Previously we demonstrated that the collagen hybridizing peptide [CHP, sequence: (GPO)9 , O: hydroxyproline] can specifically recognize the degraded and unfolded collagen chains through triple helix formation...
August 22, 2018: Biomaterials
Kanisht Batra, Aman Kumar, Sushila Maan, Vinay Kumar, Rajni Kumari, Trilok Nanda
Early and accurate diagnosis of pregnancy in animals is important for improving the reproductive management of livestock. The buffalo (Bubalus bubalis) is the most important dairy animal in India, but there are reproductive problems resulting from extended calving interval and ovulation occurring in the absence of behavioral estrus. The lack of simple methods for early pregnancy diagnosis intensifies these problems. The present study, therefore, was conducted to ascertain the role of the interferon-stimulated gene, (ISG), 15 in pregnancy detection...
October 2018: Animal Reproduction Science
Christian Steinebach, Stefanie Lindner, Namrata D Udeshi, Deepak C Mani, Hannes Kehm, Simon Köpff, Steven A Carr, Michael Gütschow, Jan Krönke
The immunomodulatory drugs (IMiDs) thalidomide, lenalidomide, and pomalidomide, all approved for the treatment of multiple myeloma, induce targeted ubiquitination and degradation of Ikaros (IKZF1) and Aiolos (IKZF3) via the cereblon (CRBN) E3 ubiquitin ligase. IMiD-based proteolysis-targeting chimeras (PROTACs) can efficiently recruit CRBN to a protein of interest, leading to its ubiquitination and proteasomal degradation. By linking two pomalidomide molecules, we designed homobifunctional, so-called homo-PROTACs and investigated their ability to induce self-directed ubiquitination and degradation...
September 5, 2018: ACS Chemical Biology
Wen-Jing Fan, Zhi-Qiao Fan, Mei-Juan Yang, Yao-Zhu Pan, Hai Bai
Cereblon(CRBN) is a brain-associated protein with ionic protease activity, which interacts with DNA damage-binding protein-1 (DDB1), Cullin 4 (Cul4A or Cul4B), and regulator of Cullins 1 (RoC1) to form the functional E3 ubiquitin ligase complex(CRBN-CRL4) that performs proteolysis via the ubiquitin-proteasome pathway. And CRBN is a necessary target protein for the anti-myeloma effect of immunomodulators. The combination of lenalidomide and CRBN recruited a new substrate that binds to the CRBN-CRL4 complex, leading to increased ubiquitination and proteasome-dependent degradation, thus resulting in anti-myeloma activity...
August 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Seyed Hamidreza Mahmoudpour, Obul Reddy Bandapalli, Miguel Inácio da Silva Filho, Chiara Campo, Kari Hemminki, Hartmut Goldschmidt, Maximilian Merz, Asta Försti
BACKGROUND: Based on the possible shared mechanisms of chemotherapy-induced peripheral neuropathy (CIPN) for different drugs, we aimed to aggregate results of all previously published genome-wide association studies (GWAS) on CIPN, and to replicate them within a cohort of multiple myeloma (MM) patients. METHODS: Following a systematic literature search, data for CIPN associated single nucleotide polymorphisms (SNPs) with P-values< 10- 5 were extracted; these associations were investigated within a cohort of 983 German MM patients treated with bortezomib, thalidomide or vincristine...
August 15, 2018: BMC Cancer
Fakhredin Saba, Masoud Soleimani, Saeid Abroun
Bone is one of the most common sites of complication in multiple myeloma (MM) progression and bone remodeling gets definitively perturbed during disease progression. Hypoxia and miR-210 play an important role in hematological malignancies. In an attempt to elucidate the specificity of the pathways of hypoxia and miR-210 in suppression of osteoblastic differentiation in MM patients, we examined the effect of miR-210 and hypoxia on expression of important cytokines and genes of myeloma cells. Differentiation of BM-MSCs towards osteoblastic cells in response to microvesicles (MVs) was also investigated...
2018: EXCLI Journal
Tae Yeul Kim, Ja-Yoon Gu, Hye Soo Jung, Youngil Koh, Inho Kim, Hyun Kyung Kim
Leukemic cells release their nuclear contents into the extracellular space upon activation. The released nuclear contents, called extracellular traps, can activate the contact system of coagulation. This study accessed the extent of contact system activation, the levels of extracellular traps, and coagulation activation in hematologic malignancies including acute leukemia. In 154 patients with hematologic malignancies (acute leukemia, n = 29; myelodysplastic syndrome, n = 20; myeloproliferative neoplasms, n = 69; plasma cell myeloma, n = 36) and 48 normal controls, the levels of coagulation factors (fibrinogen and factor VII, VIII, IX, and XII), D-dimer, thrombin generation, extracellular trap markers (histone-DNA complex, cell-free dsDNA, leukocyte elastase), and contact system markers (activated factor XII [XIIa], high-molecular-weight kininogen, prekallikrein, bradykinin) were measured...
October 2018: Journal of Thrombosis and Thrombolysis
Zheng Chen, Tsung-Chin Lin, Xiaohong Bi, Guijin Lu, Brian C Dawson, Roberto Miranda, L Jeffrey Medeiros, Ian McNiece, Nami McCarty
Despite progress in the treatment of MM, including the use of high-dose chemotherapy and autologous stem cell transplantation, a considerable proportion of patients are refractory to all therapies. This resistance is related to the molecular genetic heterogeneity in MM cells as well as to the contributions from the BM, which is one of the key determinants of treatment outcome. Our previous studies using fluorescent tracers revealed that MM heterogeneity is correlated with the presence of quiescent stem-like cancer cells, which prefer to reside within the osteoblastic niche of the BM...
August 8, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Masturah Bte Mohd Abdul Rashid, Tan Boon Toh, Lissa Hooi, Aleidy Silva, Yanzhou Zhang, Pei Fang Tan, Ai Ling Teh, Neerja Karnani, Sudhakar Jha, Chih-Ming Ho, Wee Joo Chng, Dean Ho, Edward Kai-Hua Chow
Multiple myeloma is an incurable hematological malignancy that relies on drug combinations for first and secondary lines of treatment. The inclusion of proteasome inhibitors, such as bortezomib, into these combination regimens has improved median survival. Resistance to bortezomib, however, is a common occurrence that ultimately contributes to treatment failure, and there remains a need to identify improved drug combinations. We developed the quadratic phenotypic optimization platform (QPOP) to optimize treatment combinations selected from a candidate pool of 114 approved drugs...
August 8, 2018: Science Translational Medicine
Marte Fauskanger, Ole Audun Werner Haabeth, Frode Miltzow Skjeldal, Bjarne Bogen, Anders Aune Tveita
CD4+ T cells can induce potent anti-tumor immune responses. Due to the lack of MHC class II expression in most cancer cells, antigen recognition occurs indirectly via uptake and presentation on tumor-infiltrating antigen-presenting cells (APCs). Activation of the APCs can induce tumor rejection, but the mechanisms underlying tumor killing by such cells have not been established. To elucidate the molecular basis of CD4+ T-cell-mediated tumor rejection, we utilized a murine model of multiple myeloma, in which the T cells recognize a secreted tumor neoantigen...
2018: Frontiers in Immunology
Melda Sarıman, Neslihan Abacı, Sema Sırma Ekmekçi, Aris Çakiris, Ferda Perçin Paçal, Duran Üstek, Mesut Ayer, Mustafa Nuri Yenerel, Sevgi Beşışık, Kıvanç Çefle, Şükrü Palandüz, Şükrü Öztürk
Background: Multiple Myeloma (MM) is plasma cell dyscrasia characterized by transformation of B cells into malignant cells. Although there are data regarding molecular pathology of multiple myeloma, molecularmechanisms of the disease has not been fully explained. Aims: To investigate gene expression profiles in bone marrow myeloma cells via RNA sequencing technology. Study Design: Cell study. Methods: Four untreated MM patients myeloma cells and 4 healthy donors B cells from bone marrow were sorted using FACSAria II...
August 6, 2018: Balkan Medical Journal
Anja Seckinger, Jens Hillengass, Martina Emde, Susanne Beck, Christoph Kimmich, Tobias Dittrich, Michael Hundemer, Anna Jauch, Ute Hegenbart, Marc-Steffen Raab, Anthony D Ho, Stefan Schönland, Dirk Hose
Monoclonal antibodies against the cell surface antigen CD38, e.g., isatuximab, daratumumab, or Mor202, have entered the therapeutic armamentarium in multiple myeloma due to single agent overall response rates of 29 vs. 36 vs. 31%, effectivity in combination regimen, e.g., with lenalidomide or bortezomib plus dexamethasone, and tolerable side effects. Despite clinical use, many questions remain. In this manuscript, we address three of these: first, upfront CD38 target-expression in AL-amyloidosis, monoclonal gammopathy of unknown significance (MGUS), asymptomatic, symptomatic, and relapsed multiple myeloma...
2018: Frontiers in Immunology
Jérôme Debus, Pierre Lemaire, Mustafa Alani, Jonathan Farhi, Johann Rose, Vincent Cussac, Sabine Defasque, Nathalie Denizon, Habib Ghnaya, Anne Besançon-Bergelin, Kamel Laribi, Fabienne Pineau-Vincent
We report here a case of lymphoplasmacytic lymphoma with IgA paraproteinemia and a case of concomitant Waldenström macroglobulinemia and monoclonal gammapathy of unknown significance. These rare cases show that the isotype of a monoclonal immunoglobulin does not allow to foresee every time the underlying pathology. Clinical data and medical imaging are essential. From a biological point of view, additional analysis such as immunophenotyping, cytogenetics and molecular biology are required in addition to the cytological features in order to make an accurate differential diagnosis between lymphoid and plasma cell malignancy...
August 1, 2018: Annales de Biologie Clinique
Youqiang Sun, Vincent Kuek, Yuhao Liu, Jennifer Tickner, Yu Yuan, Leilei Chen, Zhikui Zeng, Min Shao, Wei He, Jiake Xu
MiR-214 belongs to a family of microRNA (small, highly conserved noncoding RNA molecules) precursors that play a pivotal role in biological functions, such as cellular function, tissue development, tissue homeostasis, and pathogenesis of diseases. Recently, miR-214 emerged as a critical regulator of musculoskeletal metabolism. Specifically, miR-214 can mediate skeletal muscle myogenesis and vascular smooth muscle cell proliferation, migration, and differentiation. MiR-214 also modulates osteoblast function by targeting specific molecular pathways and the expression of various osteoblast-related genes; promotes osteoclast activity by targeting phosphatase and tensin homolog (Pten); and mediates osteoclast-osteoblast intercellular crosstalk via an exosomal miRNA paracrine mechanism...
August 4, 2018: Journal of Cellular Physiology
Cyrille Touzeau, Paulo Maciag, Martine Amiot, Philippe Moreau
Despite advances in the treatment of multiple myeloma, the disease still remains incurable for the majority of patients. The overexpression of anti-apoptotic proteins (i.e., Bcl-2, Bcl-XL or Mcl-1) is a hallmark of cancer and favors tumor cell survival and resistance to therapy. The oral drug venetoclax is the first-in-class Bcl-2-specific BH3 mimetic. In myeloma, in vitro sensitivity to venetoclax is mainly observed in plasma cells harboring the t(11;14) translocation, a molecular subgroup associated with high Bcl-2 and low Mcl-1/Bcl-XL expression...
September 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Phaik Ju Teoh, Omer An, Tae-Hoon Chung, Jing Yuan Chooi, Sabrina H M Toh, Shuangyi Fan, Wilson Wang, Bryan T H Koh, Melissa J Fullwood, Melissa G Ooi, Sanjay de Mel, Cinnie Y Soekojo, Leilei Chen, Siok Bian Ng, Henry Yang, Wee Joo Chng
DNA alterations have been extensively reported in multiple myeloma (MM); however, they cannot yet fully explain all the biological and molecular abnormalities in MM, which remains till this day an incurable disease with eventual emergence of refractory disease. Recent years have seen abnormalities at the RNA levels being reported to possess potential biological relevance in cancers. ADAR1-mediated-A-to-I-editing is an important post-transcriptional mechanism in human physiology and the biological implication of its abnormality, especially at the global level, is underexplored in MM...
July 30, 2018: Blood
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