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https://www.readbyqxmd.com/read/28916317/presence-of-human-herpesvirus-8-hhv-8-dna-sequences-in-patients-with-lymphoproliferative-diseases-and-chronic-blood-disorders
#1
Hossein Keyvani, Mohammad Hadi Karbalaie Niya, Maryam Esghaei, Farah Bokharaei Salim, Seyed Hamid Reza Monavari
OBJECTIVE: Human herpesvirus 8 (HHV-8) is the causative agent of Kaposi's sarcoma (KS), but it has also been associated with different hematologic malignancies, including plasmablastic lymphoma, Multicentric Castleman's disease (MCD), primary effusion lymphoma (PEL) and various atypical lymphoproliferative disorders. Patients with underlying lymphoproliferative diseases and chronic blood disorders who become infected with this virus are at risk for human malignancies. This small study reported the frequency of human herpesvirus -8 in 81 Iranian patients with lymphoproliferative disorders for estimation of possible factors affecting malignancy...
September 12, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28916311/lenalidomide-maintenance-after-first-line-therapy-for-high-risk-chronic-lymphocytic-leukaemia-cllm1-final-results-from-a-randomised-double-blind-phase-3-study
#2
Anna Maria Fink, Jasmin Bahlo, Sandra Robrecht, Othman Al-Sawaf, Ali Aldaoud, Holger Hebart, Kathleen Jentsch-Ullrich, Steffen Dörfel, Kirsten Fischer, Clemens-Martin Wendtner, Thomas Nösslinger, Paolo Ghia, Francesc Bosch, Arnon P Kater, Hartmut Döhner, Michael Kneba, Karl-Anton Kreuzer, Eugen Tausch, Stephan Stilgenbauer, Matthias Ritgen, Sebastian Böttcher, Barbara Eichhorst, Michael Hallek
BACKGROUND: The combined use of genetic markers and detectable minimal residual disease identifies patients with chronic lymphocytic leukaemia with poor outcome after first-line chemoimmunotherapy. We aimed to assess lenalidomide maintenance therapy in these high-risk patients. METHODS: In this randomised, double-blind, phase 3 study (CLLM1; CLL Maintenance 1 of the German CLL Study Group), patients older than 18 years and diagnosed with immunophenotypically confirmed chronic lymphocytic leukaemia with active disease, who responded to chemoimmunotherapy 2-5 months after completion of first-line therapy and who were assessed as having a high risk for an early progression with at least a partial response after four or more cycles of first-line chemoimmunotherapy, were eligible if they had high minimal residual disease levels or intermediate levels combined with an unmutated IGHV gene status or TP53 alterations...
September 12, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28915641/reevaluation-of-atr-signaling-in-primary-resting-chronic-lymphocytic-leukemia-cells-evidence-for-pro-survival-or-pro-apoptotic-function
#3
Maxime Beyaert, Eliza Starczewska, Ana Cristina González Pérez, Nicolas Vanlangendonck, Pascale Saussoy, Gaëlle Tilman, Anne De Leener, Marie-Christiane Vekemans, Eric Van Den Neste, Françoise Bontemps
ATM, primarily activated by DNA double-strand breaks, and ATR, activated by single-stranded DNA, are master regulators of the cellular response to DNA damage. In primary chronic lymphocytic leukemia (CLL) cells, ATR signaling is considered to be switched off due to ATR downregulation. Here, we hypothesized that ATR, though expressed at low protein level, could play a role in primary resting CLL cells after genotoxic stress. By investigating the response of CLL cells to UV-C irradiation, a prototypical activator of ATR, we could detect phosphorylation of ATR at Thr-1989, a marker for ATR activation, and also observed that selective ATR inhibitors markedly decreased UV-C-induced phosphorylation of ATR targets, including H2AX and p53...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28905668/the-impact-of-agent-orange-exposure-on-prognosis-and-management-in-patients-with-chronic-lymphocytic-leukemia-a-national-veteran-affairs-tumor-registry-study
#4
Craig Mescher, David Gilbertson, Nicole M Randall, Gobind Tarchand, Julie Tomaska, Lisa Baumann Kreuziger, Vicki A Morrison
Exposure to Agent Orange (AO) has been associated with the development of chronic lymphocytic leukemia (CLL). We performed a retrospective study of 2052 Vietnam veterans identified in the National VA Tumor Registry to assess the impact of AO exposure on CLL prognosis, treatment and survival. Prognostic factors did not differ based on exposure. Veterans exposed to AO were diagnosed younger (63.2 vs. 70.5 years, p < .0001) and had longer overall survival (median not reached vs. 91 months, p < .001)...
September 14, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28903739/evolving-dna-methylation-and-gene-expression-markers-of-b-cell-chronic-lymphocytic-leukemia-are-present-in-pre-diagnostic-blood-samples-more-than-10%C3%A2-years-prior-to-diagnosis
#5
Panagiotis Georgiadis, Irene Liampa, Dennie G Hebels, Julian Krauskopf, Aristotelis Chatziioannou, Ioannis Valavanis, Theo M C M de Kok, Jos C S Kleinjans, Ingvar A Bergdahl, Beatrice Melin, Florentin Spaeth, Domenico Palli, R C H Vermeulen, J Vlaanderen, Marc Chadeau-Hyam, Paolo Vineis, Soterios A Kyrtopoulos
BACKGROUND: B-cell chronic lymphocytic leukemia (CLL) is a common type of adult leukemia. It often follows an indolent course and is preceded by monoclonal B-cell lymphocytosis, an asymptomatic condition, however it is not known what causes subjects with this condition to progress to CLL. Hence the discovery of prediagnostic markers has the potential to improve the identification of subjects likely to develop CLL and may also provide insights into the pathogenesis of the disease of potential clinical relevance...
September 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28903342/patients-with-chronic-lymphocytic-leukemia-and-complex-karyotype-show-an-adverse-outcome-even-in-absence-of-tp53-atm-fish-deletions
#6
Anna Puiggros, Rosa Collado, Maria José Calasanz, Margarita Ortega, Neus Ruiz-Xivillé, Alfredo Rivas-Delgado, Elisa Luño, Teresa González, Blanca Navarro, MaDolores García-Malo, Alberto Valiente, José Ángel Hernández, María Teresa Ardanaz, María Ángeles Piñan, María Laura Blanco, María Hernández-Sánchez, Ana Batlle-López, Rocío Salgado, Marta Salido, Ana Ferrer, Pau Abrisqueta, Eva Gimeno, Eugènia Abella, Christelle Ferrá, María José Terol, Francisco Ortuño, Dolors Costa, Carol Moreno, Félix Carbonell, Francesc Bosch, Julio Delgado, Blanca Espinet
Genomic complexity identified by chromosome banding analysis (CBA) predicts a worse clinical outcome in CLL patients treated either with standard or new treatments. Herein, we analyzed the clinical impact of complex karyotypes (CK) with or without high-risk FISH deletions (ATM and/or TP53, HR-FISH) in a cohort of 1045 untreated MBL/CLL patients. In all, 99/1045 (9.5%) patients displayed a CK. Despite ATM and TP53 deletions were more common in CK (25% vs 7%; P < 0.001; 40% vs 5%; P < 0.001, respectively), only 44% (40/90) patients with TP53 deletions showed a CK...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902633/ginkgetin-inhibits-proliferation-of-human-leukemia-cells-via-the-tnf-%C3%AE-signaling-pathway
#7
Ling-Ling Pan, Wen-Jun Wu, Gao-Feng Zheng, Xiao-Yan Han, Jing-Song He, Zhen Cai
Ginkgetin is known to be an anticancer agent in many studies. However, its effectiveness in treating chronic lymphoblastic leukemia (CLL) remains unknown. The present study aimed to evaluate the effects of ginkgetin on the growth of the K562 cell line. The MTT assay was employed to examine the proliferation of K562, and a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining was conducted to detect the apoptotic rates. Furthermore, changes of tumor necrosis factor-α (TNF-α) were detected by Western blot analysis...
September 13, 2017: Zeitschrift Für Naturforschung. C, A Journal of Biosciences
https://www.readbyqxmd.com/read/28899929/pathogen-specific-b-cell-receptors-drive-chronic-lymphocytic-leukemia-by-light-chain-dependent-cross-reaction-with-autoantigens
#8
Nereida Jiménez de Oya, Marco De Giovanni, Jessica Fioravanti, Rudolf Übelhart, Pietro Di Lucia, Amleto Fiocchi, Stefano Iacovelli, Dimitar G Efremov, Federico Caligaris-Cappio, Hassan Jumaa, Paolo Ghia, Luca G Guidotti, Matteo Iannacone
Several lines of evidence indirectly suggest that antigenic stimulation through the B-cell receptor (BCR) supports chronic lymphocytic leukemia (CLL) development. In addition to self-antigens, a number of microbial antigens have been proposed to contribute to the selection of the immunoglobulins expressed in CLL. How pathogen-specific BCRs drive CLL development remains, however, largely unexplored. Here, we utilized mouse models of CLL pathogenesis to equip B cells with virus-specific BCRs and study the effect of antigen recognition on leukemia growth...
September 12, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28893099/obinutuzumab-for-the-treatment-of-chronic-lymphocytic-leukemia-and-other-b-cell-lymphoproliferative-disorders
#9
Rabih Said, Apostolia M Tsimberidou
Chemoimmunotherapeutic regimens using the anti-CD20 antibody rituximab improved significantly the survival rates in various B-cell lymphoproliferative disorders (LPDs), including chronic lymphocytic leukemia (CLL). The next-generation CD20 antibody obinutuzumab represents an addition to the drug armamentarium used for the therapeutic management of patients with LPDs. Areas covered: Herein, the authors discuss the biochemical and conformational engineering of obinutuzumab to increase antibody-dependent cell-mediated cytotoxicity and direct cell death...
September 11, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28892161/a-gene-is-known-by-the-company-it-keeps-enrichment-of%C3%A2-tnfaip3%C3%A2-gene-aberrations-in-malt-lymphomas-expressing-ighv4-34-antigen-receptors
#10
Andreas Agathangelidis, Aliki Xochelli, Kostas Stamatopoulos
Associations between immunoglobulin (IG) receptors with distinctive immunogenetic features and particular gene mutations is a recurring theme in mature B cell lymphomas. Relevant observations have been made in chronic lymphocytic leukemia (CLL), where gene mutations are distributed asymmetrically in cases bearing or not somatic hypermutations within the clonotypic immunoglobulin heavy chain variable region (IGHV) genes (e.g. TP53 mutations predominate in IG-unmutated CLL, whereas the opposite is seen for MYD88 mutations, enriched in IG-mutated CLL) and in subsets of cases with stereotyped IG (enrichment for SF3B1 mutations in CLL subset #2)...
September 11, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28891959/the-pi3k%C3%AE-inhibitor-idelalisib-inhibits-homing-in-an-in-vitro-and-in-vivo-model-of-b-all
#11
Etai Adam, Hye Na Kim, Eun Ji Gang, Caitlin Schnair, Solomon Lee, Solah Lee, Sajad Khazal, Osanna Kosoyan, Marina Konopleva, Chintan Parekh, Deepa Bhojwani, Alan S Wayne, Hisham Abdel-Azim, Nora Heisterkamp, Yong-Mi Kim
The quest continues for targeted therapies to reduce the morbidity of chemotherapy and to improve the response of resistant leukemia. Adhesion of acute lymphoblastic leukemia (ALL) cells to bone marrow stromal cells triggers intracellular signals that promote cell-adhesion-mediated drug resistance (CAM-DR). Idelalisib, an U.S. Food and Drug Administration (FDA)-approved PI3Kδ-specific inhibitor has been shown to be effective in CLL in down-regulating p-Akt and prolonging survival in combination with Rituximab; herein we explore the possibility of its use in B ALL and probe the mechanism of action...
September 10, 2017: Cancers
https://www.readbyqxmd.com/read/28891366/efficacy-and-safety-of-b-cell-receptor-signaling-pathway-inhibitors-in-relapsed-refractory-chronic-lymphocytic-leukemia-a-systematic-review-and-meta-analysis-of-randomized-clinical-trials
#12
Anna Puła, Konrad Stawiski, Marcin Braun, Elżbieta Iskierka-Jażdżewska, Tadeusz Robak
Ibrutinib and idelalisib, B-cell receptor (BCR) signaling pathway inhibitors, have been recently approved for use against relapsed/refractory chronic lymphocytic leukemia (CLL). To assess the efficacy and safety of BCR pathway inhibitors in relapsed/refractory CLL, we conducted a systematic review and meta-analysis of five randomized controlled trials (1866 patients). Our study demonstrated that BCR pathway inhibitors significantly prolonged progression-free survival (PFS; pooled HR = 0.24; 95% CI: 0.19-0...
September 11, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28888994/chronic-lymphocytic-leukemia-with-isochromosome-17q-an-aggressive-subgroup-associated-with-tp53-mutations-and-complex-karyotypes
#13
Rosa Collado, Anna Puiggros, José Antonio López-Guerrero, Ma José Calasanz, Ma José Larráyoz, David Ivars, Zaida García-Casado, Eugènia Abella, Ma Teresa Orero, Elisabet Talavera, Ana Carla Oliveira, Jesús Ma Hernández-Rivas, María Hernández-Sánchez, Elisa Luño, Alberto Valiente, Javier Grau, Inmaculada Portal, Santiago Gardella, Anna Camino Salgado, Ma Teresa Giménez, Ma Teresa Ardanaz, Andrea Campeny, José Julio Hernández, Sara Álvarez, Blanca Espinet, Félix Carbonell
Although i(17q) [i(17q)] is frequently detected in hematological malignancies, few studies have assessed its clinical role in chronic lymphocytic leukemia (CLL). We recruited a cohort of 22 CLL patients with i(17q) and described their biological characteristics, mutational status of the genes TP53 and IGHV and genomic complexity. Furthermore, we analyzed the impact of the type of cytogenetic anomaly bearing the TP53 defect on the outcome of CLL patients and compared the progression-free survival (PFS) and overall survival (OS) of i(17q) cases with those of a group of 38 CLL patients harboring other 17p aberrations...
September 6, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28884705/cryptochrome-1-gene-expression-is-a-reliable-prognostic-indicator-in-egyptian-patients-with-chronic-lymphocytic-leukemia-a-cohort-prospective-study
#14
Deena Mohamed Habashy, Deena Samir Eissa, Mona Mahmoud Aboelez
Objectives Traditional prognostic factors have proven insufficient to account for the observed heterogeneity in the clinical behavior of chronic lymphocytic leukemia (CLL). Cryptochrome-1 (CRY-1) is a circadian clock gene essential in maintaining circadian rhythm and regulating cell proliferation. We evaluated CRY-1 gene expression in CLL patients, and assessed its putative role as a prognostic indicator for the clinical course of CLL. Materials and Methods Hundred CLL patients at diagnosis were studied for CRY-1 gene expression by qRT-PCR, and were followed up for assessment of time to first treatment (TFT)...
September 8, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/28882083/regulation-of-mapk-signaling-and-implications-in-chronic-lymphocytic-leukemia
#15
Ashima Shukla, Vipul Shukla, Shantaram S Joshi
Chronic lymphocytic leukemia (CLL) is a heterogeneous B cell malignancy that still remains incurable. Recent studies have highlighted cellular and non-cellular components of the tissue microenvironment in CLL that help nurture the growth of leukemic cells by providing the necessary stimuli for their proliferation and survival. The diverse stimuli in the specialized tissue microenvironment of CLL lead to constitutive activation of several signaling pathways that includes B cell receptor signaling and the associated mitogen-activated protein kinase (MAPK) signaling...
September 7, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28882002/tumor-phylogeny-inference-using-tree-constrained-importance-sampling
#16
Gryte Satas, Benjamin J Raphael
Motivation: A tumor arises from an evolutionary process that can be modeled as a phylogenetic tree. However, reconstructing this tree is challenging as most cancer sequencing uses bulk tumor tissue containing heterogeneous mixtures of cells. Results: We introduce P robabilistic A lgorithm for S omatic Tr ee I nference (PASTRI), a new algorithm for bulk-tumor sequencing data that clusters somatic mutations into clones and infers a phylogenetic tree that describes the evolutionary history of the tumor...
July 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28881739/a-phase-i-trial-of-azacitidine-and-nanoparticle-albumin-bound-paclitaxel-in-patients-with-advanced-or-metastatic-solid-tumors
#17
Adam L Cohen, Abhijit Ray, Matthew Van Brocklin, David M Burnett, Randy C Bowen, Donna L Dyess, Thomas W Butler, Theresa Dumlao, Hung T Khong
BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC), an albumin-binding protein, is downregulated by hypermethylation in many cancers. Hypomethylating agents such as azacitidine can upregulate SPARC in tumors, which may enhance the accumulation of albumin-bound drugs at tumor site. The objectives of this phase I trial was to determine the safety and maximum tolerated dose and to assess any clinical activity of the combination of azacytidine and weekly nanoparticle-albumin-bound (nab®) paclitaxel...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881725/nurse-like-cells-promote-cll-survival-through-lfa-3-cd2-interactions
#18
Frédéric Boissard, Marie Tosolini, Laetitia Ligat, Anne Quillet-Mary, Frederic Lopez, Jean-Jacques Fournié, Loic Ysebaert, Mary Poupot
In the tumoral micro-environment (TME) of chronic lymphocytic leukemia (CLL), nurse-like cells (NLC) are tumor-associated macrophages which play a critical role in the survival and chemoresistance of tumoral cells. This pro-survival activity is known to involve soluble factors, but few data are available on the relative role of cells cross-talk. Here, we used a transcriptome-based approach to systematically investigate the expression of various receptor/ligand pairs at the surface of NLC/CLL cells. Their relative contribution to CLL survival was assessed both by fluorescent microscopy to identify cellular interactions and by the use of functional tests to measure the impact of uncoupling these pairs with blocking monoclonal antibodies...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28869483/obinutuzumab-plus-chlorambucil-in-a-patient-with-severe-myasthenia-gravis-and-chronic-lymphocytic-leukemia
#19
Angela Russell, Megan Yaraskavitch, Daniel Fok, Sameer Chhibber, Lesley Street, Lawrence Korngut
Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction, characterized by fatigable weakness of the extraocular, bulbar, and limb musculature; prevalence is estimated at 14 to 32 per 100,000 in North America. Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults, resulting from clonal expansion of B-cells in blood, marrow, and secondary lymphoid tissues. The simultaneous presentation of MG and CLL is exceedingly rare. This article presents the case of 71-year-old man diagnosed simultaneously with MG and CLL...
2017: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/28867658/identification-and-characterization-of-a-potent-and-biologically-active-pde4-7-inhibitor-via-fission-yeast-based-assays
#20
Ana Santos de Medeiros, Arlene R Wyman, Manal A Alaamery, Christina Allain, F Douglas Ivey, Lili Wang, Hai Le, James P Morken, Alawi Habara, Cuong Le, Shuaiying Cui, Adam Lerner, Charles S Hoffman
We previously constructed a collection of fission yeast strains that express various mammalian cyclic nucleotide phosphodiesterases (PDEs) and developed a cell-based high throughput screen (HTS) for small molecule PDE inhibitors. Here we describe a compound, BC54, that is a selective inhibitor of enzymes from the cAMP-specific PDE4 and PDE7 families. Consistent with the biological effect of other PDE4 and PDE7 inhibitors, BC54 displays potent anti-inflammatory properties and is superior to a combination of rolipram (a PDE4 inhibitor) and BRL50481 (a PDE7A inhibitor) for inducing apoptosis in chronic lymphocytic leukemia (CLL) cells...
September 1, 2017: Cellular Signalling
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