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https://www.readbyqxmd.com/read/29239593/clinical-significance-of-gene-defects-in-b-cell-lymphomas
#1
Annika Pasanen, Leo Meriranta, Sirpa Leppä
Lymphomas are a heterogenous group of malignant diseases. Identification of sub-groups has created pressure for a more detailed diagnosis and individualized treatment. Although the underlying genetic and molecular pathologic factors of the most common B-cell derived lymphomas, i.e. diffuse large B-cell lymphoma and follicular lymphoma, have become more accurate, prognosis is evaluated and treatment options still selected mainly on the basis of clinical variables. In the future, new generation sequencing methods that are becoming more common in clinical practice will allow the assessment of prognosis and treatment on the basis of biologic and genetic risk factors...
2017: Duodecim; Lääketieteellinen Aikakauskirja
https://www.readbyqxmd.com/read/29237063/spectrum-of-pig-a-mutations-in-t-lymphocytes-of-rats-treated-with-procarbazine
#2
Javier Revollo, Javed A Bhalli, Cameron Tebbe, Jessica Noteboom, Demetria Thomas, Page McKinzie, Nicholas Felton, Mason G Pearce, Vasily N Dobrovolsky
Procarbazine is a primary component of antineoplastic combination chemotherapy often used for the treatment of Hodgkin's lymphoma. It is believed that cytostatic and cytotoxic properties of procarbazine are mediated via its interaction with genomic DNA. Procarbazine is a carcinogen in animal models; it is classified as Group 2A compound by IARC. Also it is known as an in vitro and in vivo mutagen and genotoxicant. However, the molecular mechanism by which procarbazine induces mutations is not thoroughly understood and the spectrum of procarbazine-induced in vivo mutations is described insufficiently...
December 8, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29235459/pi3k%C3%AE-activates-e2f1-synthesis-in-response-to-mrna-translation-stress
#3
Sivakumar Vadivel Gnanasundram, Slovénie Pyndiah, Chrysoula Daskalogianni, Kate Armfield, Karin Nylander, Joanna B Wilson, Robin Fåhraeus
The c-myc oncogene stimulates ribosomal biogenesis and protein synthesis to promote cellular growth. However, the pathway by which cells sense and restore dysfunctional mRNA translation and how this is linked to cell proliferation and growth is not known. We here show that mRNA translation stress in cis triggered by the gly-ala repeat sequence of Epstein-Barr virus (EBV)-encoded EBNA1, results in PI3Kδ-dependent induction of E2F1 mRNA translation with the consequent activation of c-Myc and cell proliferation...
December 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29232880/the-genome-of-the-northern-sea-otter-enhydra-lutris-kenyoni
#4
Samantha J Jones, Martin Haulena, Gregory A Taylor, Simon Chan, Steven Bilobram, René L Warren, S Austin Hammond, Karen L Mungall, Caleb Choo, Heather Kirk, Pawan Pandoh, Adrian Ally, Noreen Dhalla, Angela K Y Tam, Armelle Troussard, Daniel Paulino, Robin J N Coope, Andrew J Mungall, Richard Moore, Yongjun Zhao, Inanc Birol, Yussanne Ma, Marco Marra, Steven J M Jones
The northern sea otter inhabits coastal waters of the northern Pacific Ocean and is the largest member of the Mustelidae family. DNA sequencing methods that utilize microfluidic partitioned and non-partitioned library construction were used to establish the sea otter genome. The final assembly provided 2.426 Gbp of highly contiguous assembled genomic sequences with a scaffold N50 length of over 38 Mbp. We generated transcriptome data derived from a lymphoma to aid in the determination of functional elements...
December 11, 2017: Genes
https://www.readbyqxmd.com/read/29222311/role-of-the-microenvironment-across-histological-subtypes-of-nhl
#5
REVIEW
Karin Tarte
Recent progress in next-generation sequencing strategies has revealed the genetic landscape of B-cell non-Hodgkin lymphoma, but the tumor microenvironment is increasingly recognized as crucial to sustaining malignant B-cell survival and growth, subclonal evolution, and drug resistance. The tumor niche is made up of a dynamic and organized network of strongly heterogeneous immune and stromal cell subsets characterized by specific phenotypic, transcriptomic, and functional features. Nonmalignant cell recruitment and plasticity are dictated by lymphoma B cells, which convert their surrounding microenvironment into a supportive niche...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222305/biology-of-cns-lymphoma-and-the-potential-of-novel-agents
#6
REVIEW
James L Rubenstein
Primary and secondary CNS lymphomas are aggressive brain tumors that pose an immense challenge to define in terms of molecular pathogenesis, as well as to effectively treat. During the past 10 years improvements in survival have been achieved with the implementation of anti-CD20 immunotherapy and optimization of dose-intensive consolidation strategies. The applications of whole-exome sequencing, comparative genomic hybridization, transcriptional profiling, and examination of the tumor microenvironment, particularly in the context of clinical investigation, provide insights that create a roadmap for the development and implementation of novel targeted agents for this disease...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29221207/chst6-mutation-screening-and-endoplasmatic-reticulum-stress-in-macular-corneal-dystrophy
#7
Liyuan Wang, Xianling Tang, Xiaolin Lv, Encheng Sun, Donglai Wu, Changlin Wang, Ping Liu
Macular corneal dystrophy (MCD) is an autosomal recessive disorder mainly caused by gene mutations of carbohydrate sulfotransferase (CHST6) leading to bilateral visual impairment. Because the mechanism underlying this degeneration remains poorly understood, we investigated molecular alterations and pathways that may be involved in MCD in this issue. Different mutation sites were screened by direct sequencing of the coding region of CHST6. In addition, we described morphological changes in MCD keratocytes by light microscopy and electron microscopy and determined the relationship between the development of this disease and the occurrence of apoptosis through flow cytometry, cell counting kit-8, colony formation assay and other experiments...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221181/analysis-of-ctcl-cell-lines-reveals-important-differences-between-mycosis-fungoides-s%C3%A3-zary-syndrome-vs-htlv-1-leukemic-cell-lines
#8
Elena Netchiporouk, Jennifer Gantchev, Matthew Tsang, Philippe Thibault, Andrew K Watters, John-Douglas Matthew Hughes, Feras M Ghazawi, Anders Woetmann, Niels Ødum, Denis Sasseville, Ivan V Litvinov
HTLV-1 is estimated to affect ~20 million people worldwide and in ~5% of carriers it produces Adult T-Cell Leukemia/Lymphoma (ATLL), which can often masquerade and present with classic erythematous pruritic patches and plaques that are typically seen in Mycosis Fungoides (MF) and Sézary Syndrome (SS), the most recognized variants of Cutaneous T-Cell Lymphomas (CTCL). For many years the role of HTLV-1 in the pathogenesis of MF/SS has been hotly debated. In this study we analyzed CTCL vs. HTLV-1+ leukemic cells...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29210102/the-use-of-droplet-digital-pcr-in-liquid-biopsies-a-highly-sensitive-technique-for-myd88-p-l265p-detection-in-cerebrospinal-fluid
#9
Laura S Hiemcke-Jiwa, Monique C Minnema, Joyce H Radersma-van Loon, N Mehdi Jiwa, Mirthe de Boer, Roos J Leguit, Roel A de Weger, Manon M H Huibers
The gold standard for diagnosis of central nervous system lymphomas still regards a stereotactic brain biopsy, with the risk of major complications for the patient. As tumor cells can be detected in cerebrospinal fluid (CSF), CSF analysis can be used as an alternative. In this respect, mutation analysis in CSF can be of added value to other diagnostic parameters such a cytomorphology and clonality analysis. A well-known example of targeted mutation analysis entails MYD88 p.(L265P) detection, which is present in the majority of Bing Neel syndrome and primary central nervous system lymphoma (PCNSL) patients...
December 6, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/29207685/excellent-response-to-chemotherapy-post-immunotherapy
#10
Ashish D Dwary, Samip Master, Abhishek Patel, Constance Cole, Richard Mansour, Glenn Mills, Nebu Koshy, Prakash Peddi, Gary Burton, Dalia Hammoud, Kavitha Beedupalli
Introduction: Immunotherapy in the form of immune checkpoint inhibitors has changed the landscape of cancer treatment. Newer monoclonal antibodies are coming up and are being tested in various cancers during different stages of treatment. With the increasing use of immune checkpoint inhibitors in the management of various types of cancers, the question is raised as to what next can be offered to a patient who has progressed on this newer treatment. Does Sequence matter? There have been reports of improved responses to chemotherapy after immunotherapy in the form of vaccines...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29198913/antibody-tumor-targeting-is-enhanced-by-cd27-agonists-through-myeloid-recruitment
#11
Anna H Turaj, Khiyam Hussain, Kerry L Cox, Matthew J J Rose-Zerilli, James Testa, Lekh N Dahal, H T Claude Chan, Sonya James, Vikki L Field, Matthew J Carter, Hyung J Kim, Jonathan J West, Lawrence J Thomas, Li-Zhen He, Tibor Keler, Peter W M Johnson, Aymen Al-Shamkhani, Stephen M Thirdborough, Stephen A Beers, Mark S Cragg, Martin J Glennie, Sean H Lim
Monoclonal antibodies (mAbs) can destroy tumors by recruiting effectors such as myeloid cells, or targeting immunomodulatory receptors to promote cytotoxic T cell responses. Here, we examined the therapeutic potential of combining a direct tumor-targeting mAb, anti-CD20, with an extended panel of immunomodulatory mAbs. Only the anti-CD27/CD20 combination provided cures. This was apparent in multiple lymphoma models, including huCD27 transgenic mice using the anti-huCD27, varlilumab. Detailed mechanistic analysis using single-cell RNA sequencing demonstrated that anti-CD27 stimulated CD8+ T and natural killer cells to release myeloid chemo-attractants and interferon gamma, to elicit myeloid infiltration and macrophage activation...
November 21, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29197725/exploring-the-selectivity-of-inhibitor-complexes-with-bcl-2-and-bcl-xl-a-molecular-dynamics-simulation-approach
#12
Naoki Wakui, Ryunosuke Yoshino, Nobuaki Yasuo, Masahito Ohue, Masakazu Sekijima
B-cell lymphoma 2 (Bcl-2) family proteins are potential drug targets in cancer and have a relatively flat and flexible binding site. ABT-199 is one of the most promising selective Bcl-2 inhibitors, and A-1155463 selectively inhibits Bcl-XL. Although the amino acid sequences of the binding sites of these two inhibitors are similar, the inhibitors selectively bind the target protein. In order to determine the origin of the selectivity of these inhibitors, we conducted molecular dynamics simulations using protein-inhibitor modeling...
November 23, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29193015/the-exomic-landscape-of-t-14-18-negative-diffuse-follicular-lymphoma-with-1p36-deletion
#13
Alberto Zamò, Jordan Pischimarov, Heike Horn, German Ott, Andreas Rosenwald, Ellen Leich
Predominantly diffuse t(14;18) negative follicular lymphoma (FL) with 1p36 deletion shows distinctive clinical, morphological and molecular features that distinguish it from classical FL. In order to investigate whether it possesses a unique mutation profile, we performed whole exome sequencing of six well-characterised cases. Our analysis showed that the mutational landscape of this subtype is largely distinct from classical FL. It appears to harbour several recurrent mutations, affecting STAT6, CREBBP and basal membrane protein genes with high frequency...
November 28, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29190913/epitope-mapping-of-spontaneous-autoantibodies-to-anaplastic-lymphoma-kinase-alk-in-non-small-cell-lung-cancer
#14
Mark M Awad, Cristina Mastini, Rafael B Blasco, Luca Mologni, Claudia Voena, Lara Mussolin, Stacy L Mach, Anika E Adeni, Christine A Lydon, Lynette M Sholl, Pasi A Jänne, Roberto Chiarle
The anaplastic lymphoma kinase (ALK) is recognized by the immune system as a tumor antigen, and preclinical evidence suggests that ALK-rearranged NSCLCs can also be successfully targeted immunologically using vaccine-based approaches. In contrast to ALK-rearranged lymphomas, the frequency and clinical significance of spontaneous ALK immune responses in patients with ALK-rearranged NSCLCs are largely unknown. We developed an enzyme-linked immunosorbent assay (ELISA) to measure anti-ALK antibody levels and mapped specific peptide epitope sequences within the ALK cytoplasmic domain in patients with non-small cell lung cancer...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29180399/diminished-microrna-29b-level-is-associated-with-brd4-mediated-activation-of-oncogenes-in-cutaneous-t-cell-lymphoma
#15
Rebecca Kohnken, Jing Wen, Bethany Mundy-Bosse, Kathleen McConnell, Ashleigh Keiter, Leah Grinshpun, Alex Hartlage, Max Yano, Betina McNeil, Nitin Chakravarti, Basem William, James E Bradner, Michael A Caligiuri, Pierluigi Porcu, Anjali Mishra
MicroRNA dysregulation is a hallmark of cutaneous T-cell lymphoma (CTCL), a uniformly fatal malignancy of skin-homing CD4+ T-cells for which there are few effective therapies. The role of microRNAs (miRs) in controlling epigenetic modifier-dependent transcriptional regulation in CTCL is unknown. In this study, we characterize a novel miR dysregulation contributing to overexpression of epigenetic reader bromodomain-containing protein 4 (BRD4). Using patient CD4+ T-cells, we show diminished levels of miR-29b compared to healthy donor cells...
November 27, 2017: Blood
https://www.readbyqxmd.com/read/29176466/the-challenge-of-next-generation-sequencing-in-a-boy-with-severe-mononucleosis-and-ebv-related-lymphoma
#16
Federico Verzegnassi, Erica Valencic, Valentina Kiren, Nagua Giurici, Anna Monica Bianco, Annalisa Marcuzzi, Diego Vozzi, Alberto Tommasini, Flavio Faletra
A severe course of infectious mononucleosis should always lead up to the suspicion of a primary immunodeficiency. We describe the case of a boy with severe mononucleosis accompanied by the development of hemophagocytic lymphohistiocytosis and lymphoma. By whole exome sequencing, we identified a mutation of uncertain significance in CTPS2, a gene closely related to CTPS1, which is involved in a primary immune deficiency with susceptibility to herpesviruses. We discuss the challenge of a correct interpretation of data from whole exome sequencing, questioning whether the CTPS2 variant found in our patient is just an incidental finding or a mutation with variable penetrance...
November 23, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29173772/clinical-characteristics-and-sequence-complexity-of-anaplastic-lymphoma-kinase-gene-fusions-in-chinese-lung-cancer-patients
#17
Hong-Xia Tian, Xu-Chao Zhang, Jin-Ji Yang, Wei-Bang Guo, Zhi-Hong Chen, Zhen Wang, Yi-Long Wu
OBJECTIVES: To investigate the clinical characteristics of anaplastic lymphoma kinase (ALK) rearrangements and sequence complexity of the ALK fusion gene in Chinese lung cancer patients. METHODS: We prospectively screened ALK rearrangements in 1474 lung cancer specimens, including 1387 cases of non-small cell lung cancer (NSCLC), 54 cases of small cell lung cancer (SCLC), and 33 cases of cancer with lung metastasis from other organs by both standard polymerase chain reaction (PCR) and rapid amplification of cDNA ends (RACE)-coupled PCR...
December 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29169317/hashclone-a-new-tool-to-quantify-the-minimal-residual-disease-in-b-cell-lymphoma-from-deep-sequencing-data
#18
Marco Beccuti, Elisa Genuardi, Greta Romano, Luigia Monitillo, Daniela Barbero, Mario Boccadoro, Marco Ladetto, Raffaele Calogero, Simone Ferrero, Francesca Cordero
BACKGROUND: Mantle Cell Lymphoma (MCL) is a B cell aggressive neoplasia accounting for about the 6% of all lymphomas. The most common molecular marker of clonality in MCL, as in other B lymphoproliferative disorders, is the ImmunoGlobulin Heavy chain (IGH) rearrangement, occurring in B-lymphocytes. The patient-specific IGH rearrangement is extensively used to monitor the Minimal Residual Disease (MRD) after treatment through the standardized Allele-Specific Oligonucleotides Quantitative Polymerase Chain Reaction based technique...
November 23, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/29167021/diffuse-large-b-cell-lymphoma
#19
REVIEW
Shaoying Li, Ken H Young, L Jeffrey Medeiros
Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma worldwide, representing approximately 30-40% of all cases in different geographic regions. Patients most often present with a rapidly growing tumour mass in single or multiple, nodal or extranodal sites. The most common type of DLBCL, designated as not otherwise specified, represents 80-85% of all cases and is the focus of this review. There are also rare types of lymphoma composed of large B-cells, in aggregate about 15-20% of all neoplasms that are sufficiently distinctive to recognise separately...
November 19, 2017: Pathology
https://www.readbyqxmd.com/read/29165368/human-protoparvoviruses
#20
REVIEW
Elina Väisänen, Yu Fu, Klaus Hedman, Maria Söderlund-Venermo
Next-generation sequencing and metagenomics have revolutionized the discovery of novel viruses. In recent years, three novel protoparvoviruses have been discovered in fecal samples of humans: bufavirus (BuV) in 2012, tusavirus (TuV) in 2014, and cutavirus (CuV) in 2016. BuV has since been studied the most, disclosing three genotypes that also represent serotypes. Besides one nasal sample, BuV DNA has been found exclusively in diarrheal feces, but not in non-diarrheal feces, suggesting a causal relationship...
November 22, 2017: Viruses
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