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https://www.readbyqxmd.com/read/29785028/the-reference-epigenome-and-regulatory-chromatin-landscape-of-chronic-lymphocytic-leukemia
#1
Renée Beekman, Vicente Chapaprieta, Núria Russiñol, Roser Vilarrasa-Blasi, Núria Verdaguer-Dot, Joost H A Martens, Martí Duran-Ferrer, Marta Kulis, François Serra, Biola M Javierre, Steven W Wingett, Guillem Clot, Ana C Queirós, Giancarlo Castellano, Julie Blanc, Marta Gut, Angelika Merkel, Simon Heath, Anna Vlasova, Sebastian Ullrich, Emilio Palumbo, Anna Enjuanes, David Martín-García, Sílvia Beà, Magda Pinyol, Marta Aymerich, Romina Royo, Montserrat Puiggros, David Torrents, Avik Datta, Ernesto Lowy, Myrto Kostadima, Maša Roller, Laura Clarke, Paul Flicek, Xabier Agirre, Felipe Prosper, Tycho Baumann, Julio Delgado, Armando López-Guillermo, Peter Fraser, Marie-Laure Yaspo, Roderic Guigó, Reiner Siebert, Marc A Martí-Renom, Xose S Puente, Carlos López-Otín, Ivo Gut, Hendrik G Stunnenberg, Elias Campo, Jose I Martin-Subero
Chronic lymphocytic leukemia (CLL) is a frequent hematological neoplasm in which underlying epigenetic alterations are only partially understood. Here, we analyze the reference epigenome of seven primary CLLs and the regulatory chromatin landscape of 107 primary cases in the context of normal B cell differentiation. We identify that the CLL chromatin landscape is largely influenced by distinct dynamics during normal B cell maturation. Beyond this, we define extensive catalogues of regulatory elements de novo reprogrammed in CLL as a whole and in its major clinico-biological subtypes classified by IGHV somatic hypermutation levels...
May 21, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29757455/cells-cytokines-chemokines-and-cancer-stress-a-biobehavioral-study-of-patients-with-chronic-lymphocytic-leukemia
#2
Barbara L Andersen, Neha Godiwala Goyal, David M Weiss, Travis D Westbrook, Kami J Maddocks, John C Byrd, Amy J Johnson
BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia, with profound disease-related cellular, humoral, and innate immune suppression. The objective of this study was to study the correlations between stress and disease-specific, negative prognostic cellular, cytokine, and chemokine markers in patients with CLL. METHODS: A single-group, observational design was used. Patients with relapsed/refractory CLL (N = 96) who were entering a phase 2 trial of an experimental therapy (ibrutinib) were studied...
May 14, 2018: Cancer
https://www.readbyqxmd.com/read/29750146/sensitive-detection-of-the-natural-killer-cell-mediated-cytotoxicity-of-anti-cd20-antibodies-and-its-impairment-by-b-cell-receptor-pathway-inhibitors
#3
Floyd Hassenrück, Eva Knödgen, Elisa Göckeritz, Safi Hasan Midda, Verena Vondey, Lars Neumann, Sylvia Herter, Christian Klein, Michael Hallek, Günter Krause
The antibody-dependent cell-mediated cytotoxicity (ADCC) of the anti-CD20 monoclonal antibodies (mAbs) rituximab and obinutuzumab against the cell line Raji and isolated CLL cells and its potential impairment by kinase inhibitors (KI) was determined via lactate dehydrogenase release or calcein retention, respectively, using genetically modified NK92 cells expressing CD16-176V as effector cells. Compared to peripheral blood mononuclear cells, recombinant effector cell lines showed substantial alloreactivity-related cytotoxicity without addition of mAbs but afforded determination of ADCC with reduced interassay variability...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29736400/the-international-prognostic-index-for-patients-with-chronic-lymphocytic-leukemia-has-the-higher-value-in-predicting-overall-outcome-compared-with-the-barcelona-brno-biomarkers-only-prognostic-model-and-the-md-anderson-cancer-center-prognostic-index
#4
Carolina Muñoz-Novas, María Poza-Santaella, Isabel González-Gascón Y Marín, María Hernández-Sánchez, Ana-Eugenia Rodríguez-Vicente, María-Stefania Infante, Cecilia Heras, María-Ángeles Foncillas, Karen Marín, Jesús-María Hernández-Rivas, José-Ángel Hernández
In recent years, new prognostic indexes (PIs) for chronic lymphocytic leukemia (CLL), which include clinical, biological, and genetic variables, have been validated, highlighting the MD Anderson Cancer Center prognostic index (MDACC PI), the CLL-international prognostic index (CLL-IPI), and the Barcelona-Brno biomarkers only prognostic model. The aim of this study is to compare the utility of these PIs in a cohort of Spanish patients. A retrospective analysis of 696 unselected CLL patients newly diagnosed and previously untreated from different Spanish institutions was performed...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29721189/assessment-of-micro-rnas-expression-in-leukemic-cells-as-prognostic-markers-in-chronic-lymphocytic-leukemia-micro-rnas-can-predict-survival-in-a-course-of-the-disease
#5
Agnieszka Szymczyk, Sylwia Chocholska, Arkadiusz Macheta, Dariusz Szczepanek, Marek Hus, Monika Podhorecka
Numerous genetic alterations predicting prognosis and clinical outcome are revealed recently in chronic lymphocytic leukemia (CLL). Among them the deregulated expression of micro RNAs that can induce tumor growth, or act as tumor suppressors seem to be of great importance. This study aimed to analyze the possible role of chosen micro RNAs as markers of prognosis in patients with CLL. We assessed the expression of miR-21, miR-34a, miR-181a, miR-199a/b and miR-221 in previously separated leukemic cells with the use of qRQ-PCR technique at the moment of diagnosis...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29720177/genomic-characterization-of-chronic-lymphocytic-leukemia-cll-in-radiation-exposed-chornobyl-cleanup-workers
#6
Juhi Ojha, Iryna Dyagil, Stuart C Finch, Robert F Reiss, Adam J de Smith, Semira Gonseth, Mi Zhou, Helen M Hansen, Amy L Sherborne, Jean Nakamura, Paige M Bracci, Nataliya Gudzenko, Maureen Hatch, Nataliya Babkina, Mark P Little, Vadim V Chumak, Kyle M Walsh, Dimitry Bazyka, Joseph L Wiemels, Lydia B Zablotska
BACKGROUND: Chronic lymphocytic leukemia (CLL) was the predominant leukemia in a recent study of Chornobyl cleanup workers from Ukraine exposed to radiation (UR-CLL). Radiation risks of CLL significantly increased with increasing bone marrow radiation doses. Current analysis aimed to clarify whether the increased risks were due to radiation or to genetic mutations in the Ukrainian population. METHODS: A detailed characterization of the genomic landscape was performed in a unique sample of 16 UR-CLL patients and age- and sex-matched unexposed general population Ukrainian-CLL (UN-CLL) and Western-CLL (W-CLL) patients (n = 28 and 100, respectively)...
May 2, 2018: Environmental Health: a Global Access Science Source
https://www.readbyqxmd.com/read/29672642/runx1-pdcd6-fusion-resulting-from-a-novel-t-5-21-p15-q22-chromosome-translocation-in-myelodysplastic-syndrome-secondary-to-chronic-lymphocytic-leukemia
#7
Ioannis Panagopoulos, Ludmila Gorunova, Eva-Marie Jacobsen, Kristin Andersen, Francesca Micci, Sverre Heim
Leukemic cells often carry chromosome aberrations which generate chimeric genes of pathogenetic, diagnostic, and prognostic importance. New rearrangements giving rise to novel fusion genes define hitherto unrecognized genetic leukemia subgroups. G-banding, fluorescence in situ hybridization (FISH), and molecular genetic analyses were done on bone marrow cells from a patient with chronic lymphocytic leukemia (CLL) and secondary myelodysplasia. The G-banding analysis revealed the karyotype 46,XX,del(21)(q22)[9]/46,XX[2]...
2018: PloS One
https://www.readbyqxmd.com/read/29666114/chronic-lymphocytic-leukemia-and-mantle-cell-lymphoma-crossroads-of-genetic-and-microenvironment-interactions
#8
Xose S Puente, Pedro Jares, Elias Campo
Chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) are two well defined entities that diverge in their basic pathogenic mechanisms and clinical evolution but they share epidemiological characteristics, cells of origin, molecular alterations, and clinical features that differ from other lymphoid neoplasms. CLL and MCL are classically considered indolent and aggressive neoplasms, respectively. However, the clinical evolution of both tumors is very heterogeneous, with subsets of patients having a stable disease for long time whereas others require immediate intervention...
April 17, 2018: Blood
https://www.readbyqxmd.com/read/29650518/secretory-igm-exacerbates-tumor-progression-by-inducing-accumulations-of-mdscs-in-mice
#9
Chih-Hang Anthony Tang, Shiun Chang, Ayumi Hashimoto, Yi-Ju Chen, Chang Won Kang, Anthony R Mato, Juan R Del Valle, Dmitry Gabrilovich, Chih-Chi Andrew Hu
Chronic lymphocytic leukemia cells can secrete immunoglobulin M. However, it is not clear whether secretory IgM (sIgM) plays a role in disease progression. We crossed the Eμ-TCL1 mouse model of CLL, in which the expression of human TCL1 oncogene was driven by the V(H) promoter-Ig(H)-Eμ enhancer, with MD4 mice whose B cells produced B cell receptor (membrane-bound IgM) and sIgM with specificity for hen egg lysozyme (HEL). CLL cells developed in these MD4/Eμ-TCL1 mice reactivated a parental Ig gene allele and secreted IgM, and did not recognize HEL...
April 12, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29547969/a-genome-wide-association-study-of-igm-antibody-against-phosphorylcholine-shared-genetics-and-phenotypic-relationship-to-chronic-lymphocytic-leukemia
#10
Xu Chen, Stefan Gustafsson, Thomas Whitington, Yan Borné, Erik Lorentzen, Jitong Sun, Peter Almgren, Jun Su, Robert Karlsson, Jie Song, Yi Lu, Yiqiang Zhan, Sara Hägg, Per Svensson, Karin E Smedby, Susan L Slager, Erik Ingelsson, Cecilia M Lindgren, Andrew P Morris, Olle Melander, Thomas Karlsson, Ulf de Faire, Kenneth Caidahl, Gunnar Engström, Lars Lind, Mikael C I Karlsson, Nancy L Pedersen, Johan Frostegård, Patrik K E Magnusson
Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWASs) in four European-ancestry cohorts, six single nucleotide polymorphisms (SNPs) in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined β = 0...
May 15, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29484684/clinical-pathological-and-biological-characterization-of-richter-syndrome-developing-after-ibrutinib-treatment-for-relapsed-chronic-lymphocytic-leukemia
#11
Idanna Innocenti, Davide Rossi, Giulio Trapè, Francesco Autore, Luigi Maria Larocca, Vincenzo Gomes, Michaela Cerri, Paolo Falcucci, Simona Sica, Gianluca Gaidano, Luca Laurenti
Richter syndrome, a transformation of chronic lymphocytic leukemia (CLL) into a diffuse large B-cell lymphoma, is a rare complication of patients treated with chemo-immunotherapy. Richter syndrome might be both clonally related or unrelated to the underlying CLL and often showed mutations of the TP53 and NOTCH1 genes. Recently, ibrutinib was approved for patients with relapsed/refractory CLL or for untreated CLL patients with del 17p or TP53 mutation. The clinical picture, pathology, and genetics of Richter transformation after IBR treatment are largely unknown...
February 27, 2018: Hematological Oncology
https://www.readbyqxmd.com/read/29483496/comparison-of-chromosomal-rearrangements-in-bone-marrow-cells-and-blast-transformed-b-cells-in-relapse-of-b-cell-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma
#12
S V Andreieva, K V Korets, O E Ruzhinska, I M Skorokhod, O G Alkhimova
AIM: The genetic mechanisms of resistance to chemotherapy in B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL) are not clear. We aimed to determine the peculiarities of abnormal karyotype formation in bone marrow (BM) cells and peripheral blood (PB) blast transformed B-cells in relapse of B-CLL/SLL. MATERIALS AND METHODS: Cytogenetic GTG banding technique and molecular cytogenetic in interphase cells (i-FISH) studies of BM cells and PB blast transformed B-lymphocytes were performed in 14 patients (10 males and 4 females) with B-CLL/SLL...
July 2017: Experimental Oncology
https://www.readbyqxmd.com/read/29460654/cumulative-experience-and-long-term-follow-up-of-pentostatin-based-chemoimmunotherapy-trials-for-patients-with-chronic-lymphocytic-leukemia
#13
Neil E Kay, Betsy R LaPlant, Adam M Pettinger, Timothy G Call, Jose F Leis, Wei Ding, Sameer A Parikh, Michael J Conte, Deborah A Bowen, Tait D Shanafelt
BACKGROUND: 7 regimens of pentostatin based chemoimmunotherapy (CIT) for progressive previously untreated CLL primarily with long term follow-up to update both efficacy and toxicity. RESEARCH DESIGN AND METHODS: Prognostic markers including assessment of IGVH and FISH status were done on all. Response rates and 95% binomial confidence intervals were calculated for each regimen and in the combined cohort. Overall survival and treatment-free survival were evaluated using Kaplan-Meier methods...
April 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29455639/role-of-bruton-s-tyrosine-kinase-in-b-cells-and-malignancies
#14
REVIEW
Simar Pal Singh, Floris Dammeijer, Rudi W Hendriks
Bruton's tyrosine kinase (BTK) is a non-receptor kinase that plays a crucial role in oncogenic signaling that is critical for proliferation and survival of leukemic cells in many B cell malignancies. BTK was initially shown to be defective in the primary immunodeficiency X-linked agammaglobulinemia (XLA) and is essential both for B cell development and function of mature B cells. Shortly after its discovery, BTK was placed in the signal transduction pathway downstream of the B cell antigen receptor (BCR). More recently, small-molecule inhibitors of this kinase have shown excellent anti-tumor activity, first in animal models and subsequently in clinical studies...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29371889/cytogenetic-mutation-profile-of-chronic-lymphocytic-leukemia-malignant-melanoma-collision-tumors-of-the-skin
#15
Roberta La Starza, Tiziana Pierini, Lorenza Pastorino, Elisa Albi, Caterina Matteucci, Barbara Crescenzi, Paolo Sportoletti, Piero Covarelli, Franca Falzetti, Giovanni Roti, Stefano Ascani, Cristina Mecucci
Background: Collision tumors are rare entities that consist of two histologically distinct tumor types arising in the same anatomic site. An association between chronic lymphocytic leukemia (CLL) and malignant melanoma (MM) has been already described. Up to now, they have been documented only at positive regional lymph nodes while we focused on collision tumor in a skin lesion. Case presentation: We characterized the genomic profile of a skin CLL/MM collision tumor in a patient with a 9-years story of CLL...
2018: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29365086/genetic-landscape-of-ultra-stable-chronic-lymphocytic-leukemia-patients
#16
S Raponi, I Del Giudice, M Marinelli, J Wang, L Cafforio, C Ilari, A Piciocchi, M Messina, S Bonina, S Tavolaro, M Bordyuh, P Mariglia, N Peragine, F R Mauro, S Chiaretti, S Molica, M Gentile, A Visentin, L Trentin, G M Rigolin, A Cuneo, F Diop, D Rossi, G Gaidano, A Guarini, R Rabadan, R Foà
Background: Chronic lymphocytic leukemia (CLL) has a heterogeneous clinical course. Beside patients requiring immediate treatment, others show an initial indolent phase followed by progression and others do not progress for decades. The latter two subgroups usually display mutated IGHV genes and a favorable FISH profile. Patients and Methods: Patients with absence of disease progression for over 10 years (11-30) from diagnosis were defined as ultra-stable CLL (US-CLL)...
January 22, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29352719/prognostic-testing-patterns-and-outcomes-of-chronic-lymphocytic-leukemia-patients-stratified-by-fluorescence-in-situ-hybridization-cytogenetics-a-real-world-clinical-experience-in-the-connect-cll-registry
#17
Anthony Mato, Chadi Nabhan, Neil E Kay, Nicole Lamanna, Thomas J Kipps, David L Grinblatt, Christopher R Flowers, Charles M Farber, Matthew S Davids, Pavel Kiselev, Arlene S Swern, Shriya Bhushan, Kristen Sullivan, E Dawn Flick, Jeff P Sharman
INTRODUCTION: Prognostic genetic testing is recommended for patients with chronic lymphocytic leukemia (CLL) to guide clinical management. Specific abnormalities, such as del(17p), del(11q), and unmutated IgHV, can predict the depth and durability of the response to CLL therapy. PATIENTS AND METHODS: In the present analysis of the Connect CLL Registry (ClinicalTrials.gov identifier, NCT01081015), a prospective observational cohort study of patients treated across 199 centers, the patterns of prognostic testing and outcomes of patients with unfavorable-risk genetics were analyzed...
February 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29286619/comparison-of-diagnostic-yield-of-a-fish-panel-against-conventional-cytogenetic-studies-for-hematological-malignancies-a-south-indian-referral-laboratory-analysis-of-201-cases
#18
Vishal Ashok, Ramya Ranganathan, Smitha Chander, Sharat Damodar, Sunil Bhat, Nataraj K S, Satish Kumar A, Sachin Suresh Jadav, Mahesh Rajashekaraiah, Sundareshan T S
Objectives: Genetic markers are crucial fort diagnostic and prognostic investigation of hematological malignancies (HM). The conventional cytogenetic study (CCS) has been the gold standard for more than five decades. However, FISH (Fluorescence in Situ Hybridization) testing has become a popular modality owing to its targeted approach and the ability to detect abnormalities in non-mitotic cells. We here aimed to compare the diagnostic yields of a FISH panel against CCS in HMs. Methods: Samples of bone marrow and peripheral blood for a total of 201 HMs were tested for specific gene rearrangements using multi-target FISH and the results were compared with those from CCS...
December 29, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29286517/distribution-of-rs2124594-genotypes-in-chronic-lymphocytic-leukemia-patients-depending-on-radiation-anamnesis
#19
N I Bilous, I V Abramenko, A A Chumak, I S Diagil, Z V Martina
OBJECTIVE: to test the method of polymerase chain reaction with following fragments' length restriction to deter mine the rs2124594 polymorphism and to study its contribution in the development of chronic lymphocytic leukemia (CLL) in the post Chornobyl period. METHODS: Genotypes of rs2124594 were determined in 109 patients with CLL of B cell origin including 53 patients irradiated due to the Chornobyl NPP accident. Genotypes distribution among CLL patients was compared with healthy persons of European origin (the 1000 Genomes Project data set was used as a reference)...
December 2017: Problemy Radiat︠s︡iĭnoï Medyt︠s︡yny Ta Radiobiolohiï
https://www.readbyqxmd.com/read/29286214/lack-of-associations-between-tlr9-and-myd88-gene-polymorphisms-and-risk-of-chronic-lymphocytic-leukemia
#20
Yasser B.M Ali, Rasha M Foad, Essam Abdel-Wahed
Background: Genetic factors like single nucleotide polymorphisms (SNPs) may play an important role in the etiology of chronic lymphocytic leukemia (CLL). Mutations in Toll like receptor 9 (TLR9) and myeloid differentiation primary response 88 (MYD88) genes may lead to an abnormal immune response that may cause greater cell proliferation and thus alter an individual’s susceptibility to haematological malignancies including CLL. Objective: This work was designed to study any association of the TLR9 (rs2066807C/G and rs187084T/C) and MYD88 (L265P) single nucleotide polymorphism (SNPs) with risk of CLL in Egyptians...
December 29, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
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