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CLL, Immunology

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https://www.readbyqxmd.com/read/29032512/il-33-signalling-in-liver-immune-cells-enhances-drug-induced-liver-injury-and-inflammation
#1
Maísa Mota Antunes, Alan Moreira Araújo, Ariane Barros Diniz, Rafaela Vaz Sousa Pereira, Débora Moreira Alvarenga, Bruna Araújo David, Renata Monti Rocha, Maria Alice Freitas Lopes, Sarah Cozzer Marchesi, Brenda Naemi Nakagaki, Érika Carvalho, Pedro Elias Marques, Bernhard Ryffel, Valérie Quesniaux, Rodrigo Guabiraba Brito, José Carlos Alves Filho, Denise Carmona Cara, Rafael Machado Rezende, Gustavo Batista Menezes
OBJECTIVE AND DESIGN: The aim of this study was to investigate the contribution of IL-33/ST2 axis in the onset and progression of acute liver injury using a mice model of drug-induced liver injury (DILI). MATERIAL AND TREATMENTS: DILI was induced by overdose administration of acetaminophen (APAP) by oral gavage in wild-type BALB/c, ST2-deficient mice and in different bone marrow chimeras. Neutrophils were depleted by anti-Ly6G and macrophages with clodronate liposomes (CLL)...
October 14, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29032274/assessment-of-impact-of-hla-type-on-outcomes-of-allogeneic-hematopoietic-stem-cell-transplantation-for-chronic-lymphocytic-leukemia
#2
Brian T Hill, Kwang Woo Ahn, Zhen-Huan Hu, Mahmoud Aljurf, Amer Beitinjaneh, Jean-Yves Cahn, Jan Cerny, Mohamed A Kharfan-Dabaja, Siddhartha Ganguly, Nilanjan Ghosh, Michael R Grunwald, Yoshihiro Inamoto, Tamila Kindwall-Keller, Taiga Nishihori, Richard F Olsson, Ayman Saad, Matthew Seftel, Sachiko Seo, Jeffrey Szer, Martin Tallman, Celalettin Ustun, Peter H Wiernik, Richard T Maziarz, Matt Kalaycio, Edwin Alyea, Uday Popat, Ronald Sobecks, Wael Saber
Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with many highly effective therapies. Chemorefractory disease, often characterized by deletion of chromosome 17p, has historically been associated with very poor outcomes, leading to the application of allogeneic hematopoietic stem cell transplantation (allo-HCT) for medically fit patients. Although the use of allo-HCT has declined since the introduction of novel targeted therapy for the treatment of CLL, there remains significant interest in understanding factors that may influence the efficacy of allo-HCT, the sole known curative treatment for CLL...
October 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28916317/presence-of-human-herpesvirus-8-hhv-8-dna-sequences-in-patients-with-lymphoproliferative-diseases-and-chronic-blood-disorders
#3
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...
October 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28833722/killing-two-birds-with-one-stone-response-to-pembrolizumab-in-a-patient-with-metastatic-melanoma-and-b-cell-chronic-lymphocytic-leukemia
#4
M Arenbergerova, A Fialova, P Arenberger, S Gkalpakiotis, T Jirasek, A Srp, A Novotna, H Frankova
Pembrolizumab, a humanized immunoglobulin G4 monoclonal antibody against PD-1, has demonstrated antitumor activity and a manageable safety profile in patients with different solid tumors and hematologic malignancies in multiple clinical trials (1-4). Although these data highlight the effectiveness of PD-1 pathway inhibition, some patients, even those with highly immunogenic tumors, such as melanoma, do not achieve objective response (1). An increased association of B-cell chronic lymphocytic leukemia (B-CLL) and melanoma, possibly related to an underlying immunologic defect, has been previously reported (5)...
August 22, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28803824/the-clinical-spectrum-of-hepatic-manifestations-in-chronic-lymphocytic-leukemia
#5
REVIEW
Natalia Kreiniz, Ofrat Beyar Katz, Aaron Polliack, Tamar Tadmor
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world, characterized by the presence of long-lived circulating leukemic cells in the peripheral blood that may infiltrate all organs, particularly those of the reticulo-endothelial system. Liver enlargement and elevation of liver enzymes related to specific involvement by the underlying disease are well-recognized features in these patients. In CLL, the differential diagnosis of liver disorders is broad and includes liver infiltration by leukemic cells, immunologic manifestations associated with CLL, primary and secondary hepatic malignancies, drug-induced hepatotoxicity, infections, and Richter transformation...
July 23, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28758262/paraneoplastic-pemphigus-seen-in-4-patients-with-hematologic-malignancies-formerly-treated-with-rituximab
#6
C Baykal, S Kılıç, R Küçükoğlu
Paraneoplastic pemphigus (PNP) is a peculiar variant of pemphigus with pathognomonic clinical, histological, and immunological features. It is typically associated with hematologic malignancies (84%), such as non-Hodgkin lymphomas (NHL) (most common), chronic lymphocytic leukemia (CLL), Castleman disease, thymoma, Waldenström's macroglobulinemia, Hodgkin lymphoma, and monoclonal gammopathy, as well as non-hematological neoplasms, such as epithelial carcinomas, mesenchymal sarcomas, and malignant melanoma. This article is protected by copyright...
July 31, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28752619/spectrum-and-immunophenotyping-of-653-patients-with-b-cell-chronic-lymphoproliferative-disorders-in-china-a-single-centre-analysis
#7
Yi Miao, Lei Cao, Qian Sun, Xiao-Tong Li, Yan Wang, Chun Qiao, Li Wang, Rong Wang, Hai-Rong Qiu, Wei Xu, Jian-Yong Li, Yu-Jie Wu, Lei Fan
The incidence of B-cell chronic lymphoproliferative disorders (B-CLPDs) is significantly lower in China than that in western countries. There have been studies involving small cohorts with conflicting results regarding the spectrum of B-CLPDs in China, and the types and immunophenotyping of B-CLPDs in China remain largely unexplored. We conducted a retrospective analysis of 653 cases of B-CLPDs seen in our centre from 2011 to 2015. Four-colour flow cytometry was used to determine the expression of each immunological marker, and the diagnostic values of the immunological markers were also investigated...
July 28, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28666691/direct-targeting-of-cancer-cells-with-antibodies-what-can-we-learn-from-the-successes-and-failure-of-unconjugated-antibodies-for-lymphoid-neoplasias
#8
REVIEW
Josée Golay
Following approval in 1997 of the anti-CD20 antibody rituximab for the treatment of B-NHL and CLL, many other unconjugated IgG1 MAbs have been tested in pre-clinical and clinical trials for the treatment of lymphoid neoplasms. Relatively few have been approved however and these are directed against a limited number of target antigens (CD20, CD52, CCR4, CD38, CD319). We review here the known biological properties of these antibodies and discuss which factors may have led to their success or may, on the contrary, limit their clinical application...
June 27, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28494631/learning-from-the-failures-of-drug-discovery-in-b-cell-non-hodgkin-lymphomas-and-perspectives-for-the-future-chronic-lymphocytic-leukemia-and-diffuse-large-b-cell-lymphoma-as-two-ends-of-a-spectrum-in-drug-development
#9
REVIEW
Boris Kubuschok, Martin Trepel
Despite substantial recent advances, there is still an unmet need for better therapies in B-cell non Hodgkin lymphomas (B-NHL), especially in relapsed or refractory disease. Many novel targeted drugs have been developed based on a better molecular understanding of B-NHL. Areas covered: This article focuses on chronic lymphocytic leukemia (CLL) as a representative for indolent lymphomas and paradigmatic for the tremendous progress in treating B-NHL on the one hand and diffuse large B-cell lymphoma (DLBCL) as a representative for aggressive lymphomas and paradigmatic for many unsolved problems in lymphoma treatment or the other hand...
July 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28295181/long-term-follow-up-of-patients-receiving-allogeneic-stem-cell-transplant-for-chronic-lymphocytic-leukaemia-mixed-t-cell-chimerism-is-associated-with-high-relapse-risk-and-inferior-survival
#10
Philip A Thompson, Francesco Stingo, Michael J Keating, William G Wierda, Susan M O'Brien, Zeev Estrov, Celina Ledesma, Katayoun Rezvani, Muzaffar Qazilbash, Nina Shah, Simrit Parmar, Uday Popat, Paolo Anderlini, Nieto Yago, Stefan O Ciurea, Partow Kebriaei, Richard Champlin, Elizabeth J Shpall, Chitra M Hosing
There is limited information regarding the immunological predictors of post-allogeneic stem cell transplant (alloSCT) outcome in chronic lymphocytic leukaemia (CLL), such as mixed T-cell chimerism. We analysed 143 consecutive patients with relapsed/refractory CLL, transplanted between 2000 and 2012, to determine the prognostic relevance of mixed chimerism post-alloSCT and the ability of post-transplant immunomodulation to treat relapse. Mixed T-cell chimerism occurred in 50% of patients at 3 months and 43% at 6 months post-alloSCT; upon 3- and 6-month landmark analysis, this was associated with inferior progression-free survival (PFS) [Hazard ratio (HR) 1·93, P = 0·003 and HR 2·58, P < 0·001] and survival (HR 1·66, P = 0·05 and HR 2·17, P < 0·001), independent of baseline patient characteristics, and a lower rate of grade II-IV acute graft-versus-host disease (GHVD) (16% vs...
May 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28096240/coevolution-of-leukemia-and-host-immune-cells-in-chronic-lymphocytic-leukemia
#11
REVIEW
Noelia Purroy, Catherine J Wu
Cumulative studies on the dissection of changes in driver genetic lesions in cancer across the course of the disease have provided powerful insights into the adaptive mechanisms of tumors in response to the selective pressures of therapy and environmental changes. In particular, the advent of next-generation-sequencing (NGS)-based technologies and its implementation for the large-scale comprehensive analyses of cancers have greatly advanced our understanding of cancer as a complex dynamic system wherein genetically distinct subclones interact and compete during tumor evolution...
April 3, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28067179/cd20-based-immunotherapy-of-b-cell-derived-hematologic-malignancies
#12
Dariush Shanehbandi, Jafar Majidi, Tohid Kazemi, Behzad Baradaran, Leili Aghebati-Maleki
CD20 is a surface antigen which is expressed at certain stages of B-cell differentiation. Targeting the CD20-positive B-cells with therapeutic monoclonal antibodies (MAbs) has been an effectual strategy in the treatment of hematologic malignancies such as non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Initial success with Rituximab (RTX) has encouraged the creation and development of more effective CD20 based therapeutics. However, treatment with conventional MAbs has not been adequate to overcome the problems such as refractory/relapsed disease...
January 9, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27890932/il-10-production-by-cll-cells-is-enhanced-in-the-anergic-ighv-mutated-subset-and-associates-with-reduced-dna-methylation-of-the-il10-locus
#13
S Drennan, A D'Avola, Y Gao, C Weigel, E Chrysostomou, A J Steele, T Zenz, C Plass, P W Johnson, A P Williams, G Packham, F K Stevenson, C C Oakes, F Forconi
Chronic lymphocytic leukemias (CLLs) with unmutated (U-CLL) or mutated (M-CLL) IGHV have variable features of immunosuppression, possibly influenced by those CLL cells activated to produce interleukin 10 (IL-10). The two subsets differ in their levels of anergy, defined by low surface immunoglobulin M levels/signaling capacity, and in their DNA methylation profile, particularly variable in M-CLL. We have now found that levels of IL-10 produced by activated CLL cells were highly variable. Levels were higher in M-CLL than in U-CLL and correlated with anergy...
August 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27890931/a-tlr7-agonist-enhances-the-antitumor-efficacy-of-obinutuzumab-in-murine-lymphoma-models-via-nk-cells-and-cd4-t-cells
#14
E J Cheadle, G Lipowska-Bhalla, S J Dovedi, E Fagnano, C Klein, J Honeychurch, T M Illidge
Anti-CD20 monoclonal antibodies (mAb) such as rituximab have been proven to be highly effective at improving outcome in B-cell malignancies. However, many patients ultimately relapse and become refractory to treatment. The glycoengineered anti-CD20 mAb obinutuzumab was developed to induce enhanced antibody-dependent cellular cytotoxicity, antibody-dependent phagocytosis and direct cell death and was shown to lead to improved outcomes in a randomized study in B-CLL. We hypothesized that immune stimulation through Toll-like receptor 7 (TLR7) agonism in combination with obinutuzumab would further enhance lymphoma clearance and the generation of long-term antitumor immune responses...
July 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27643996/simultaneous-existence-of-acute-myeloid-leukemia-and-chronic-lymphocytic-leukemia-a-case-report
#15
Eman Al Mussaed, Hani Osman, Ghaleb Elyamany
BACKGROUND: The simultaneous Occurrence of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) has been rarely reported. Most of these cases have been occurring more frequently as a secondary event in patients receiving chemotherapeutic agents for CLL. CASE PRESENTATION: We describe a case of a 77-year-old man who presented with fatigue, pallor and lower limb pain and weakness. Initial laboratory studies showed Hb 7.7 g/dl, WBC 279.6 × 10(9)/1, PLT 143× 10(9)/1...
September 19, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27630324/malakoplakia-of-the-urinary-bladder-in-a-patient-with-chronic-lymphocytic-leukemia-under-ibrutinib-therapy-a-case-report
#16
Sotirios Sachanas, Gerassimos A Pangalis, Petros Karouzakis, Efstathios Koulieris, Maria Moschogiannis, Christina Kalpadakis, Xanthi Yiakoumis, Dimitra Rontogianni
Malakoplakia, a rare granulomatous disease of infectious etiology, is commonly observed in immunocompromised patients. Chronic lymphocytic leukemia (CLL) is characterized by profound immune dysregulation resulting in significant infection-related morbidity and mortality, and several drugs used in CLL treatment have a severe immunosuppressive effect. Ibrutinib, has become a new standard-of-care in patients with CLL, especially for those harboring unfavorable genetic characteristics such as 17 p deletion, with however, unknown long-term immunological consequences...
September 2016: Anticancer Research
https://www.readbyqxmd.com/read/27531597/histopathologic-spectrum-of-hypersensitivity-reactions-associated-with-anti-cd52-therapy-alemtuzumab
#17
Stacie L Clark, Julie Y Tse, David C Fisher, Nicole R LeBeouf, George F Murphy, Thomas S Kupper, Rachael A Clark, Christine G Lian
BACKGROUND: Alemtuzumab is a humanized monoclonal antibody directed against CD52, a cell surface antigen on B and T lymphocytes, and used to treat B-cell chronic lymphocytic leukemia and cutaneous T-cell lymphoma. Skin rash is a common adverse reaction following treatment with alemtuzumab. However, the clinicopathologic features and immunologic basis for the reaction have not been previously reported. METHODS: Our hospital's electronic pathology database was searched for cases with documentation of 'alemtuzumab' or 'anti-CD52' in the clinical history provided by either the ordering physician or the pathologist...
November 2016: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/27499044/cd5-expression-promotes-il-10-production-through-activation-of-the-mapk-erk-pathway-and-upregulation-of-trpc1-channels-in-b-lymphocytes
#18
Soizic Garaud, Taher E Taher, Marjolaine Debant, Miguel Burgos, Sarra Melayah, Christian Berthou, Kaushal Parikh, Jacques-Olivier Pers, Damien Luque-Paz, Gilles Chiocchia, Maikel Peppelenbosch, David A Isenberg, Pierre Youinou, Olivier Mignen, Yves Renaudineau, Rizgar A Mageed
CD5 is constitutively expressed on T cells and a subset of mature normal and leukemic B cells in patients with chronic lymphocytic leukemia (CLL). Important functional properties are associated with CD5 expression in B cells, including signal transducer and activator of transcription 3 activation, IL-10 production and the promotion of B-lymphocyte survival and transformation. However, the pathway(s) by which CD5 influences the biology of B cells and its dependence on B-cell receptor (BCR) co-signaling remain unknown...
August 8, 2016: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/27402426/secondary-immunodeficiency-in-lymphoproliferative-malignancies
#19
REVIEW
Vanda Friman, Ola Winqvist, Cecilie Blimark, Petra Langerbeins, Helen Chapel, Fatima Dhalla
Secondary immunodeficiencies occur as a consequence of various diseases, including hematological malignancies, and the use of pharmacological therapies, such as immunosuppressive, anti-inflammatory, and biological drugs. Infections are the main cause of morbidity and mortality in multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients. Recent advances in treatment have prolonged the duration of remission and the time between relapse phases in MM and CLL patients. However, managing multiple relapses and the use of salvage therapies can lead to cumulative immunosuppression and a higher risk of infections...
September 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27252234/phenotype-and-immune-function-of-lymph-node-and-peripheral-blood-cll-cells-are-linked-to-transendothelial-migration
#20
Marta Pasikowska, Elisabeth Walsby, Benedetta Apollonio, Kirsty Cuthill, Elizabeth Phillips, Eve Coulter, Maria Serena Longhi, Yun Ma, Deborah Yallop, Linda D Barber, Piers Patten, Chris Fegan, Alan G Ramsay, Chris Pepper, Stephen Devereux, Andrea G S Buggins
Several lines of evidence suggest that homing of tumor cells to lymphoid tissue contributes to disease progression in chronic lymphocytic leukemia (CLL). Here, we demonstrate that lymph node (LN)-derived CLL cells possess a distinct phenotype, and exhibit enhanced capacity for T-cell activation and superior immune synapse formation when compared with paired peripheral blood (PB) samples. LN-derived CLL cells manifest a proliferative, CXCR4(dim)CD5(bright) phenotype compared with those in the PB and higher expression of T-cell activation molecules including CD80, CD86, and HLA-D-related (DR)...
July 28, 2016: Blood
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