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CLL, Immunology

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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
#1
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 (CLL) with unmutated (U-CLL) or mutated (M-CLL) IGHV have variable features of immunosuppression, possibly influenced by those CLL cells activated to produce IL-10. The two subsets differ in their levels of anergy, defined by low surface IgM 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...
November 28, 2016: 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-anti-tumor-efficacy-of-obinutuzumab-in-murine-lymphoma-models-via-nk-cells-and-cd4-t-cells
#2
E J Cheadle, G Lipowska-Bhalla, S J Dovedi, E Fagnano, C Klein, J Honeychurch, T M Illidge
Anti-CD20 mAb such as rituximab have proven 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-chronic lymphocytic leukemia (B-CLL). We hypothesized that immune stimulation through TLR7 agonism in combination with obinutuzumab would further enhance lymphoma clearance and the generation of long-term anti-tumor immune responses...
November 28, 2016: 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
#3
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...
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
#4
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
#5
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...
August 17, 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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/27154182/addition-of-rice-bran-arabinoxylan-to-curcumin-therapy-may-be-of-benefit-to-patients-with-early-stage-b-cell-lymphoid-malignancies-monoclonal-gammopathy-of-undetermined-significance-smoldering-multiple-myeloma-or-stage-0-1-chronic-lymphocytic-leukemia-a-preliminary
#9
Terry Golombick, Terrence H Diamond, Arumugam Manoharan, Rajeev Ramakrishna
Hypothesis Prior studies on patients with early B-cell lymphoid malignancies suggest that early intervention with curcumin may lead to delay in progressive disease and prolonged survival. These patients are characterized by increased susceptibility to infections. Rice bran arabinoxylan (Ribraxx) has been shown to have immunostimulatory, anti-inflammatory, and proapoptotic effects. We postulated that addition of Ribraxx to curcumin therapy may be of benefit. Study design Monoclonal gammopathy of undetermined significance (MGUS)/smoldering multiple myeloma (SMM) or stage 0/1 chronic lymphocytic leukemia (CLL) patients who had been on oral curcumin therapy for a period of 6 months or more were administered both curcumin (as Curcuforte) and Ribraxx...
June 2016: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/27118451/extracellular-vesicles-released-by-cd40-il-4-stimulated-cll-cells-confer-altered-functional-properties-to-cd4-t-cells
#10
Dawn T Smallwood, Benedetta Apollonio, Shaun Willimott, Larissa Lezina, Afaf Alharthi, Ashley R Ambrose, Giulia De Rossi, Alan G Ramsay, Simon D Wagner
The complex interplay between cancer cells, stromal cells, and immune cells in the tumor microenvironment (TME) regulates tumorigenesis and provides emerging targets for immunotherapies. Crosstalk between CD4(+) T cells and proliferating chronic lymphocytic leukemia (CLL) tumor B cells occurs within lymphoid tissue pseudofollicles, and investigating these interactions is essential to understand both disease pathogenesis and the effects of immunotherapy. Tumor-derived extracellular vesicle (EV) shedding is emerging as an important mode of intercellular communication in the TME...
July 28, 2016: Blood
https://www.readbyqxmd.com/read/26153226/emerging-immunological-drugs-for-chronic-lymphocytic-leukemia
#11
REVIEW
Pawel Robak, Piotr Smolewski, Tadeusz Robak
INTRODUCTION: Over the last few years, several new immunological drugs, particularly monoclonal antibodies (mAbs), immunomodulatory drugs and B-cell receptor (BCR) pathway inhibitors have been developed and investigated in chronic lymphocytic leukemia (CLL). This article summarizes recent discoveries regarding their mechanism of action, pharmacological properties, clinical activity and toxicity, as well as the emerging role of these agents in CLL. AREAS COVERED: A literature review of mAbs, BCR pathway inhibitors and immunomodulating drugs was conducted of the MEDLINE database via PubMed for articles in English...
September 2015: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/26095886/immunotherapy-in-acute-myeloid-leukemia
#12
REVIEW
Dolores A Grosso, Rosemary C Hess, Mark A Weiss
Despite the remarkable progress made in some leukemias such as CML and CLL, cytotoxic treatment for AML remains essentially unchanged over the last 4 decades. Several lines of evidence, including the graft versus leukemia effect associated with allogeneic hematopoietic stem cell transplantation (HSCT), suggest that immunotherapy is an active modality in AML. Given the lack of progress for chemotherapy in this disease, many novel immunologic treatment approaches have been explored. The goals of non-transplant-based immune approaches have largely consisted of the stimulation or restoration of endogenous immune responses or the targeting of specific tumor antigens by immune cells...
August 15, 2015: Cancer
https://www.readbyqxmd.com/read/26084672/perturbation-of-the-normal-immune-system-in-patients-with-cll
#13
REVIEW
Francesco Forconi, Paul Moss
Immune dysregulation is a cardinal feature of chronic lymphocytic leukemia (CLL) from its early stage and worsens during clinical observation, even in absence of disease progression. Although the mechanisms remain unclear, new insights are emerging into the complex relationship between the CLL clone and its immune environment. T cells are increased in early-stage disease and show progressive accumulation and exhaustion. The mechanisms that drive this expansion may include auto-antigens involved in the original clonal expansion...
July 30, 2015: Blood
https://www.readbyqxmd.com/read/25972916/aberrant-epstein-barr-virus-antibody-patterns-and-chronic-lymphocytic-leukemia-in-a-spanish-multicentric-case-control-study
#14
Delphine Casabonne, Yolanda Benavente, Claudia Robles, Laura Costas, Esther Alonso, Eva Gonzalez-Barca, Adonina Tardón, Trinidad Dierssen-Sotos, Eva Gimeno Vázquez, Marta Aymerich, Elias Campo, Gemma Castaño-Vinyals, Nuria Aragones, Marina Pollan, Manolis Kogevinas, Hedy Juwana, Jaap Middeldorp, Silvia de Sanjose
BACKGROUND: Epstein-Barr virus (EBV)-related malignancies harbour distinct serological responses to EBV antigens. We hypothesized that EBV serological patterns can be useful to identify different stages of chronic lymphocytic leukemia. METHODS: Information on 150 cases with chronic lymphocytic leukemia and 157 frequency-matched (by age, sex and region) population-based controls from a Spanish multicentre case-control study was obtained. EBV immunoglobulin G serostatus was evaluated through a peptide-based ELISA and further by immunoblot analysis to EBV early antigens (EA), nuclear antigen (EBNA1), VCA-p18, VCA-p40 and Zebra...
2015: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/25956014/advances-in-basic-and-clinical-immunology-in-2014
#15
REVIEW
Javier Chinen, Luigi D Notarangelo, William T Shearer
Genetic identification of immunodeficiency syndromes has become more efficient with the availability of whole-exome sequencing, expediting the identification of relevant genes and complementing traditional linkage analysis and homozygosity mapping. New genes defects causing immunodeficiency include phophoglucomutase 3 (PGM3), cytidine 5' triphosphate synthase 1 (CTPS1), nuclear factor κB-inducing kinase (NIK), cytotoxic T lymphocyte-associated antigen 4 (CTLA4), B-cell chronic lymphocytic leukemia/lymphoma 10 (BCL10), phosphoinositide-3 kinase regulatory subunit 1 (PIK3R1), IL21, and Jagunal homolog 1 (JAGN1)...
May 2015: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/25917633/an-update-on-current-and-prospective-immunotherapies-for-chronic-lymphocytic-leukemia
#16
REVIEW
Josephine N Emole, Frederick L Locke, Javier Pinilla-Ibarz
Chronic lymphocytic leukemia (CLL) is the most common leukemia. Combined agent chemotherapy is the current standard front-line treatment for physically fit patients with CLL. Use of chemotherapy can be complicated by significant toxicity, especially in patients with advanced age or comorbid conditions. Moreover, patients may relapse and become refractory to further chemotherapy. Immunotherapy targets the aberrant immunological processes in CLL without the toxicity of chemotherapy. Immunotherapeutic strategies can also be combined with chemotherapy to improve response rates in this incurable disease...
2015: Immunotherapy
https://www.readbyqxmd.com/read/25800048/pd-l1-checkpoint-blockade-prevents-immune-dysfunction-and-leukemia-development-in-a-mouse-model-of-chronic-lymphocytic-leukemia
#17
Fabienne McClanahan, Bola Hanna, Shaun Miller, Andrew James Clear, Peter Lichter, John G Gribben, Martina Seiffert
Blockade of the programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint augments antitumor immunity and induces durable responses in patients with solid cancers, but data on clinical efficacy in leukemias are sparse. Chronic lymphocytic leukemia (CLL) is associated with a tumor-supportive microenvironment and a dysfunctional immune system, as shown by "exhausted" T cells, defective immunologic synapse formation, and immunosuppressive myeloid cells. These defects involve aberrant expression of PD-L1 and are closely mirrored in the Eµ-TCL1 mouse model for CLL...
July 9, 2015: Blood
https://www.readbyqxmd.com/read/25696844/mutations-in-chronic-lymphocytic-leukemia-and-how-they-affect-therapy-choice-focus-on-notch1-sf3b1-and-tp53
#18
REVIEW
Clive S Zent, W Richard Burack
Chronic lymphocytic leukemia (CLL) is characterized by a relatively small number of recurrent genetic defects. These can be evaluated by clinically available methods such as fluorescent in situ hybridization and targeted sequencing approaches to provide data that can be very helpful in prognostication and planning of treatment. Acquired defects in the p53 pathway, activating mutations of NOTCH1, and dysfunctional mutations of SF3B1 and BIRC3 identify patients with higher risk of progressive disease, poorer responses to conventional chemoimmunotherapy, and shorter survival...
December 5, 2014: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/25541495/the-mystery-of-chronic-lymphocytic-leukemia-cll-why-is-it-absent-in-asians-and-what-does-this-tell-us-about-etiology-pathogenesis-and-biology
#19
REVIEW
Shen-Miao Yang, Jian-Yong Li, Robert Peter Gale, Xiao-Jun Huang
Chronic lymphocytic leukemia/small lymphocytic lymphoma is common in persons of predominately European descent but rare in Asians. Why is unknown but is likely genetically-determined. Environmental factors may also operate but are likely to be less important. When CLL occurs in Asians it has different features than CLL in persons of predominately European descent. The reason(s) for this is also not understood. We reviewed data on CLL in Asians (mostly Han Chinese but also other ethnic groups) and compared these data with those from persons of predominately European descent with CLL...
May 2015: Blood Reviews
https://www.readbyqxmd.com/read/25468260/the-top-ten-clues-to-understand-the-origin-of-chronic-lymphocytic-leukemia-cll
#20
REVIEW
Ricardo García-Muñoz, Jesús Feliu, Luis Llorente
The fundamental task of the immune system is to protect the individual from infectious organisms without serious injury to self. The essence of acquired immunity is molecular self/non self discrimination. Chronic lymphocytic leukemia is characterized by a global failure of immune system that begins with the failure of immunological tolerance mechanisms (autoimmunity) and finish with the incapacity to response to non-self antigens (immunodeficiency). Immunological tolerance mechanisms are involved in chronic lymphocytic leukemia (CLL) development...
January 2015: Journal of Autoimmunity
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