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https://www.readbyqxmd.com/read/28710251/role-for-zap-70-signaling-in-the-differential-effector-functions-of-rituximab-and-obinutuzumab-ga101-in-chronic-lymphocytic-leukemia-b-cells
#1
Sladjana Skopelja-Gardner, Jonathan D Jones, B JoNell Hamilton, Alexey V Danilov, William F C Rigby
Rituximab (RTX) has been the hallmark anti-CD20 mAb for the treatment of B cell neoplasms, including B cell chronic lymphocytic leukemia (B-CLL). Recently, a novel humanized anti-CD20 mAb obinutuzumab (GA101) has been implemented as first-line CLL therapy. Treatment of CLL patients with RTX is associated with CD20 loss via an FcγR-mediated process, trogocytosis. RTX-induced trogocytosis has been characterized as both the means of resistance to therapy, via loss of cell surface target proteins (antigenic modulation), as well as a process that alters B cell phenotype and function...
July 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28708284/cd20-specific-immunoligands-engaging-nkg2d-enhance-%C3%AE-%C3%AE-t-cell-mediated-lysis-of-lymphoma-cells
#2
Matthias Peipp, Daniela Wesch, Hans-Heinrich Oberg, Sebastian Lutz, Anja Muskulus, Jan G J van de Winkel, Paul W H I Parren, Renate Burger, Andreas Humpe, Dieter Kabelitz, Martin Gramatzki, Christian Kellner
Human γδ T cells are innate-like T cells which are able to kill a broad range of tumor cells and thus may have potential for cancer immunotherapy. The activating receptor natural killer group 2 member D (NKG2D) plays a key role in regulating immune responses driven by γδ T cells. Here, we explored whether recombinant immunoligands consisting of a CD20 single-chain fragment variable (scFv) linked to a NKG2D ligand, either MHC class I chain-related protein A (MICA) or UL16 binding protein 2 (ULBP2), could be employed to engage γδ T cells for tumor cell killing...
July 14, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28694085/baseline-characteristics-predicting-very-good-outcome-of-allogeneic-hematopoietic-cell-transplantation-in-young-patients-with-high-cytogenetic-risk-chronic-lymphocytic-leukemia%C3%A2-a-retrospective-analysis-from-the-chronic-malignancies-working-party-of-the-ebmt
#3
Michel van Gelder, Dimitris Ziagkos, Liesbeth de Wreede, Anja van Biezen, Peter Dreger, Martin Gramatzki, Matthias Stelljes, Niels Smedegaard Andersen, Nicolaas Schaap, Antonin Vitek, Dietrich Beelen, Vesa Lindström, Jürgen Finke, Jacob Passweg, Matthias Eder, Maciej Machaczka, Julio Delgado, William Krüger, Luděk Raida, Gerard Socié, Pavel Jindra, Boris Afanasyev, Eva Wagner, Yves Chalandon, Anja Henseler, Stefan Schoenland, Nicolaus Kröger, Johannes Schetelig
BACKGROUND: Patients with genetically high-risk relapsed/refractory chronic lymphocytic leukemia have shorter median progression-free survival (PFS) with kinase- and BCL2-inhibitors (KI, BCL2i). Allogeneic hematopoietic stem cell transplantation (alloHCT) may result in sustained PFS, especially in younger patients because of its age-dependent non-relapse mortality (NRM) risk, but outcome data are lacking for this population. PATIENTS AND METHODS: Risk factors for 2-year NRM and 8-year PFS were identified in patients < 50 years in an updated European Society for Blood and Marrow Transplantation registry cohort (n = 197; median follow-up, 90...
June 17, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28687625/a-phase-ii-trial-evaluating-the-safety-of-rapid-infusion-of-ofatumumab-in-patients-with-previously-treated-chronic-lymphocytic-leukemia
#4
William Donnellan, Jesus G Berdeja, Diana Shipley, Edward R Arrowsmith, David Wright, Scott Lunin, Richard Brown, James H Essell, Ian W Flinn
LESSONS LEARNED: Ofatumumab infusion reactions can be diminished by escalating the dose rate in individual patients in sequential infusions. BACKGROUND: Ofatumumab (OFA) is a fully humanized, anti-CD20 antibody approved for use in chronic lymphocytic leukemia (CLL). The recommended administration requires long infusion times. We evaluated an accelerated infusion regimen of 2 hours. METHODS: The first dose of OFA (300 mg) was given on week 1 day 1 starting at 3...
July 7, 2017: Oncologist
https://www.readbyqxmd.com/read/28680761/the-splenic-marginal-zone-shapes-the-phenotype-of-leukemia-b-cells-and-facilitates-their-niche-specific-retention-and-survival
#5
Vanessa Stache, Lydia Verlaat, Marcel Gätjen, Kristina Heinig, Jörg Westermann, Armin Rehm, Uta E Höpken
Microenvironmental regulation in lymphoid tissues is essential for the development of chronic lymphocytic leukemia. We identified cellular and molecular factors provided by the splenic marginal zone (MZ), which alter the migratory and adhesive behavior of leukemic cells. We used the Cxcr5(-/-)Eµ-Tcl1 leukemia mouse model, in which tumor cells are excluded from B cell follicles and instead accumulate within the MZ. Genes involved in MZ B cell development and genes encoding for adhesion molecules were upregulated in MZ-localized Cxcr5(-/-)Eµ-Tcl1 cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28679298/prevalence-of-cutaneous-viral-infections-in-incident-cutaneous-squamous-cell-carcinoma-detected-among-chronic-lymphocytic-leukemia-and-hematopoietic-stem-cell-transplant-patients
#6
Shalaka S Hampras, Frederick L Locke, Julio C Chavez, Nishit S Patel, Anna R Giuliano, Kyle Miller, Tarik Gheit, Massimo Tommasino, Dana E Rollison
The role of cutaneous viral infections in the development of non-melanoma skin cancer (NMSC), including cutaneous squamous cell carcinoma (SCC), among chronic lymphocytic leukemia (CLL) and blood and marrow transplant (BMT) patients is not established. CLL (n = 977) and BMT (n = 3587) patients treated at the Moffitt Cancer Center were included in a retrospective cohort study. Human papillomavirus (HPV) and human polyomavirus (HPyV) DNA were examined in a subset of incident SCC tumors. Five-year cumulative incidence of NMSC was 1...
July 6, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28676343/treatment-of-acute-myeloid-leukemia-with-t-cells-expressing-chimeric-antigen-receptors-directed-to-c-type-lectin-like-molecule-1
#7
Haruko Tashiro, Tim Sauer, Thomas Shum, Kathan Parikh, Maksim Mamonkin, Bilal Omer, Rayne H Rouce, Premal Lulla, Cliona M Rooney, Stephen Gottschalk, Malcolm K Brenner
The successful immunotherapy of acute myeloid leukemia (AML) has been hampered because most potential antigenic targets are shared with normal hematopoietic stem cells (HSCs), increasing the risk of sustained and severe hematopoietic toxicity following treatment. C-type lectin-like molecule 1 (CLL-1) is a membrane glycoprotein expressed by >80% of AML but is absent on normal HSCs. Here we describe the development and evaluation of CLL-1-specific chimeric antigen receptor T cells (CLL-1.CAR-Ts) and we demonstrate their specific activity against CLL-1(+) AML cell lines as well as primary AML patient samples in vitro...
July 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28674892/surface-profiling-of-extracellular-vesicles-from-plasma-or-ascites-fluid-using-dotscan-antibody-microarrays
#8
Larissa Belov, Susannah Hallal, Kieran Matic, Jerry Zhou, Sandra Wissmueller, Nuzhat Ahmed, Sumaiya Tanjil, Stephen P Mulligan, O Giles Best, Richard J Simpson, Richard I Christopherson
DotScan antibody microarrays were initially developed for the extensive surface profiling of live leukemia and lymphoma cells. DotScan's diagnostic capability was validated with an extensive clinical trial using mononuclear cells from the blood or bone marrow of leukemia or lymphoma patients. DotScan has also been used for the profiling of surface proteins on peripheral blood mononuclear cells (PBMC) from patients with HIV, liver disease, and stable and progressive B-cell chronic lymphocytic leukemia (CLL)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28669130/review-of-the-clinical-pharmacokinetics-and-pharmacodynamics-of-alemtuzumab-and-its-use-in-kidney-transplantation
#9
REVIEW
Marieke van der Zwan, Carla C Baan, Teun van Gelder, Dennis A Hesselink
Alemtuzumab is a humanized monoclonal antibody against CD52 and causes depletion of T and B lymphocytes, monocytes, and NK cells. Alemtuzumab is registered for the treatment of multiple sclerosis (MS) and is also used in chronic lymphocytic leukemia (CLL). Alemtuzumab is used off-label in kidney transplantation as induction and anti-rejection therapy. The objective of this review is to present a review of the pharmacokinetics, pharmacodynamics, and use of alemtuzumab in kidney transplantation. A systematic literature search was conducted using Ovid Medline, Embase, and Cochrane Central Register of controlled trials...
July 1, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28666010/dysregulation-of-h-aca-ribonucleoprotein-components-in-chronic-lymphocytic-leukemia
#10
Patricia Carolina Dos Santos, Julieta Panero, Carmen Stanganelli, Virginia Palau Nagore, Flavia Stella, Raimundo Bezares, Irma Slavutsky
Telomeres are protective repeats of TTAGGG sequences located at the end of human chromosomes. They are essential to maintain chromosomal integrity and genome stability. Telomerase is a ribonucleoprotein complex containing an internal RNA template (hTR) and a catalytic subunit (hTERT). The human hTR gene consists of three major domains; among them the H/ACA domain is essential for telomere biogenesis. H/ACA ribonucleoprotein (RNP) complex is composed of four evolutionary conserved proteins, including dyskerin (encoded by DKC1 gene), NOP10, NHP2 and GAR1...
2017: PloS One
https://www.readbyqxmd.com/read/28659152/idelalisib-may-have-the-potential-to-increase-radiotherapy-side-effects
#11
Thomas Gryc, Florian Putz, Nicole Goerig, Sonia Ziegler, Rainer Fietkau, Luitpold V Distel, Barbara Schuster
INTRODUCTION: Idelalisib is approved for the treatment of relapsed chronic lymphocytic leukemia together with Rituximab and for monotherapy of follicular B-cell non-Hodgkin's lymphoma and small lymphocytic lymphoma. It is a potent and selective phosphatidylinositol 3-kinase-δ (PI3K-δ) inhibitor. PI3K-δ primarily is expressed in B-cells and prevents effectively proliferation in malignant B-cells. METHODS: We provide a detailed report on treatment history and photo documentation of acute adverse effects of radiation therapy with simultaneous Idelalisib medication in one case of B-CLL...
June 28, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28658265/enhanced-cdc-of-b-cell-chronic-lymphocytic-leukemia-cells-mediated-by-rituximab-combined-with-a-novel-anti-complement-factor-h-antibody
#12
Mark T Winkler, Ryan T Bushey, Elizabeth B Gottlin, Michael J Campa, Eross S Guadalupe, Alicia D Volkheimer, J Brice Weinberg, Edward F Patz
Rituximab therapy for B cell chronic lymphocytic leukemia (B-CLL) has met with mixed success. Among several factors to which resistance can be attributed is failure to activate complement dependent cytotoxicity (CDC) due to protective complement regulatory proteins, including the soluble regulator complement factor H (CFH). We hypothesized that rituximab killing of non-responsive B-CLL cells could be augmented by a novel human monoclonal antibody against CFH. The B cells from 11 patients with B-CLL were tested ex vivo in CDC assays with combinations of CFH monoclonal antibody, rituximab, and a negative control antibody...
2017: PloS One
https://www.readbyqxmd.com/read/28653191/microrna-dysregulation-to-identify-novel-therapeutic-targets
#13
Carlo M Croce
This paper describes how we discovered the juxtaposition of the MYC gene to the human immunoglobulin loci and how that finding was extended to characterize molecularly the t(14;18) chromosome translocation of follicular lymphoma and to clone the BCL2 gene. BCL2 is also overexpressed in CLL, the most common human leukemia. We discovered that most of human CLLs have a deletion of two microRNAs residing in the same polycistronic RNA, miR-15a and miR-16-1, and that these two microRNAs are negative regulators of BCL2...
June 27, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28632812/systemic-interferon-alfa-injections-for-the-treatment-of-a-giant-orf
#14
Sumeyre Seda Ertekin, Mehmet Salih Gurel, Aslı Vefa Turgut Erdemir, Cem Leblebici
Orf is a zoonotic infection caused by a parapoxvirus and is endemic in sheep and goats. It may be transmitted to humans by direct contact with infected animals. We report a case of a giant orf in a patient with chronic lymphocytic leukemia (CLL), which proliferated dramatically after surgical excision and resolved after systemic interferon alfa-2a injections.
May 2017: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/28599250/evaluation-of-mir-15a-and-mir-16-1-as-prognostic-biomarkers-in-chronic-lymphocytic-leukemia
#15
REVIEW
Tatiane Vieira Braga, Fernanda Cristina Gontijo Evangelista, Lorena Caixeta Gomes, Sérgio Schusterschitz da Silva Araújo, Maria das Graças Carvalho, Adriano de Paula Sabino
Chronic lymphocytic leukemia (CLL) is a B lineage neoplasm, characterized by the accumulation of B lymphocytes of great longevity, and usually develops as a result of the inhibition of apoptosis. Clinical evolution is extremely variable amongst affected individuals with survival ranging from a few months in aggressive cases, to a few decades in cases of indolent CLL. The identification of new prognostic factors, apart from clinical staging, has been an important research topic aiming at a better understanding of CLL...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28586310/effective-control-of-acute-myeloid-leukaemia-and-acute-lymphoblastic-leukaemia-progression-by-telomerase-specific-adoptive-t-cell-therapy
#16
Sara Sandri, Francesco De Sanctis, Alessia Lamolinara, Federico Boschi, Ornella Poffe, Rosalinda Trovato, Alessandra Fiore, Sara Sartori, Andrea Sbarbati, Attilio Bondanza, Simone Cesaro, Mauro Krampera, Maria T Scupoli, Michael I Nishimura, Manuela Iezzi, Silvia Sartoris, Vincenzo Bronte, Stefano Ugel
Telomerase (TERT) is a ribonucleoprotein enzyme that preserves the molecular organization at the ends of eukaryotic chromosomes. Since TERT deregulation is a common step in leukaemia, treatments targeting telomerase might be useful for the therapy of hematologic malignancies. Despite a large spectrum of potential drugs, their bench-to-bedside translation is quite limited, with only a therapeutic vaccine in the clinic and a telomerase inhibitor at late stage of preclinical validation. We recently demonstrated that the adoptive transfer of T cell transduced with an HLA-A2-restricted T-cell receptor (TCR), which recognize human TERT with high avidity, controls human B-cell chronic lymphocytic leukaemia (B-CLL) progression without severe side-effects in humanized mice...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28580304/significance-of-inactivated-genes-in-leukemia-pathogenesis-and-prognosis
#17
REVIEW
Nazanin Heidari, Saeid Abroun, Jessika Bertacchini, Tina Vosoughi, Fakher Rahim, Najmaldin Saki
Epigenetic and genetic alterations are two mechanisms participating in leukemia, which can inactivate genes involved in leukemia pathogenesis or progression. The purpose of this review was to introduce various inactivated genes and evaluate their possible role in leukemia pathogenesis and prognosis. By searching the mesh words "Gene, Silencing AND Leukemia" in PubMed website, relevant English articles dealt with human subjects as of 2000 were included in this study. Gene inactivation in leukemia is largely mediated by promoter's hypermethylation of gene involving in cellular functions such as cell cycle, apoptosis, and gene transcription...
2017: Cell Journal
https://www.readbyqxmd.com/read/28578024/hexamerization-enhanced-cd20-antibody-mediates-complement-dependent-cytotoxicity-in-serum-genetically-deficient-in-c9
#18
Ronald P Taylor, Margaret A Lindorfer, Erika M Cook, Frank J Beurskens, Janine Schuurman, Paul W H I Parren, Clive S Zent, Karl R VanDerMeid, Richard Burack, Masashi Mizuno, B Paul Morgan
We examined complement-dependent cytotoxicity (CDC) by hexamer formation-enhanced CD20 mAb Hx-7D8 of patient-derived chronic lymphocytic leukemia (CLL) cells that are relatively resistant to CDC. CDC was analyzed in normal human serum (NHS) and serum from an individual genetically deficient for C9. Hx-7D8 was able to kill up to 80% of CLL cells in complete absence of C9. We conclude that the narrow C5b-8 pores formed without C9 are sufficient for CDC due to efficient antibody-mediated hexamer formation. In the absence of C9, we observed transient intracellular increases of Ca(2+) during CDC (as assessed with FLUO-4) that were extended in time...
May 31, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28577901/functional-studies-of-chronic-lymphocytic-leukemia-b-cells-expressing-%C3%AE-2-integrin-type-complement-receptors-cr3-and-cr4
#19
Barbara Uzonyi, Bernadett Mácsik-Valent, Szilvia Lukácsi, Richárd Kiss, Katalin Török, Mariann Kremlitzka, Zsuzsa Bajtay, Judit Demeter, Csaba Bödör, Anna Erdei
The expression and role of CR3 (CD11b/CD18) and CR4 (CD11c/CD18) in B cells are not yet explored in contrast to myeloid cells, where these β2-integrin type receptors are known to participate in various cellular functions, including phagocytosis, adherence and migration. Here we aimed to reveal the expression and role of CR3 and CR4 in human B cells. In B cells of healthy donors CR3 and CR4 are scarcely expressed. However, two patients with chronic lymphocytic leukemia (CLL) characterized by a peculiar immune-phenotype containing both CD5-positive and CD5-negative B cell populations made possible to study these molecules in distinct B cell subsets...
May 31, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28566736/aberrant-splicing-of-the-tumor-suppressor-cyld-promotes-the-development-of-chronic-lymphocytic-leukemia-via-sustained-nf-%C3%AE%C2%BAb-signaling
#20
M Hahn, J-P Bürckert, C A Luttenberger, S Klebow, M Hess, M Al-Maarri, M Vogt, S Reißig, M Hallek, A Wienecke-Baldacchino, T Buch, C P Muller, C P Pallasch, F T Wunderlich, A Waisman, N Hövelmeyer
The pathogenesis of chronic lymphocytic leukemia (CLL) has been linked to constitutive NF-κB activation but the underlying mechanisms are poorly understood. Here we show that alternative splicing of the negative regulator of NF-κB and tumor suppressor gene CYLD regulates the pool of CD5(+) B-cells through sustained canonical NF-κB signaling. Reinforced canonical NF-κB activity leads to the development of B1 cell-associated tumor formation in aging mice by promoting survival and proliferation of CD5(+) B-cells, highly reminiscent of human B-CLL...
June 1, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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