Abstract:
:Recombinant erythropoietin (EPO) and iron substitution are a standard of care for treatment of anemias associated with chronic inflammation, including anemia of chronic kidney disease. A black box warning for EPO therapy and concerns about negative side effects related to high-dose iron supplementation as well as the significant proportion of patients becoming EPO resistant over time explains the medical need to define novel strategies to ameliorate anemia of chronic disease (ACD). As hepcidin is central to the iron-restrictive phenotype in ACD, therapeutic approaches targeting hepcidin were recently developed. We herein report the therapeutic effects of a fully human anti-BMP6 antibody (KY1070) either as monotherapy or in combination with Darbepoetin alfa on iron metabolism and anemia resolution in 2 different, well-established, and clinically relevant rodent models of ACD. In addition to counteracting hepcidin-driven iron limitation for erythropoiesis, we found that the combination of KY1070 and recombinant human EPO improved the erythroid response compared with either monotherapy in a qualitative and quantitative manner. Consequently, the combination of KY1070 and Darbepoetin alfa resulted in an EPO-sparing effect. Moreover, we found that suppression of hepcidin via KY1070 modulates ferroportin expression on erythroid precursor cells, thereby lowering potentially toxic-free intracellular iron levels and by accelerating erythroid output as reflected by increased maturation of erythrocyte progenitors. In summary, we conclude that treatment of ACD, as a highly complex disease, becomes more effective by a multifactorial therapeutic approach upon mobilization of endogenous iron deposits and stimulation of erythropoiesis.
journal_name
Bloodjournal_title
Bloodauthors
Petzer V,Tymoszuk P,Asshoff M,Carvalho J,Papworth J,Deantonio C,Bayliss L,Wake MS,Seifert M,Brigo N,Valente de Souza L,Hilbe R,Grubwieser P,Demetz E,Dichtl S,Volani C,Berger S,Böhm F,Hoffmann A,Pfeifhofer-Obermair Cdoi
10.1182/blood.2019004653subject
Has Abstractpub_date
2020-08-27 00:00:00pages
1080-1090issue
9eissn
0006-4971issn
1528-0020pii
456038journal_volume
136pub_type
杂志文章相关文献
BLOOD文献大全abstract::PRKAR1A (R1A)-retinoic acid receptor-alpha (R1A-RARalpha) is the sixth RARalpha-containing fusion protein in acute promyelocytic leukemia (APL). Using the murine bone-marrow retroviral transduction/transformation assay, we showed that R1A-RARalpha fusion protein could transform bone-marrow progenitor/stem cells. In ge...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-07-232652
更新日期:2010-01-21 00:00:00
abstract::Affinity purified anticardiolipin antibodies (ACLA) raised in rabbits showed cross-reactivities with various negatively charged phospholipids as shown by both the solid phase enzyme-linked immunosorbent assay (ELISA) and inhibition studies. In ELISA, ACLA showed strong cross-reactivity to both sphingomyelin (SM) and p...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-12-15 00:00:00
abstract::Ras-associated autoimmune leukoproliferative disorder (RALD) is a chronic, nonmalignant condition that presents with persistent monocytosis and is often associated with leukocytosis, lymphoproliferation, and autoimmune phenomena. RALD has clinical and laboratory features that overlap with those of juvenile myelomonocy...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2014-11-567917
更新日期:2015-04-30 00:00:00
abstract::Interactions between P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) mediate the earliest "rolling" of leukocytes on the lumenal surface of endothelial cells at sites of inflammation. Previously, PSGL-1 has been shown to be the primary mediator of interactions between neutrophils and P-selectin, but studies o...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::Epithelial mesenchymal transitions are a remarkable example of cellular plasticity. These transitions are the hallmark of embryo development, are pivotal in cancer progression, and seem to occur infrequently in adult organisms. The reduced incidence of transitions in the adult could result from restrictive functions o...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2003-08-2807
更新日期:2004-04-15 00:00:00
abstract::Heme biosynthesis was examined in erythroid tissue of a 4-yr-old girl with severe sideroblastic anemia since infancy, as documented by the presence of intramitochondrial deposits of iron in erythroblasts. Free red cell protoporphyrin, urinary porphyrins, and activities of erythrocyte porphobilinogen synthase, uroporph...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1980-01-01 00:00:00
abstract::Salivary gland mucosa-associated lymphoid tissue (MALT) type lymphomas are typically indolent B-cell neoplasms that are often associated with Sjogren's syndrome. To better define the cell of origin and evaluate whether antigen receptor stimulation may be playing a role in tumor growth, the Ig heavy and light chain var...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-05-01 00:00:00
abstract::To test the efficacy of poststorage bedside leucodepletion of blood products in the prevention of primary HLA alloimmunization and its clinical sequelae, 172 patients with hematologic malignancy requiring intensive red blood cell and platelet support were randomized to receive either standard or filtered red blood cel...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1994-05-15 00:00:00
abstract::Rh(o)(D) immune globulin intravenous (anti-D IGIV) was licensed by the United States Food and Drug Administration (FDA) in March 1995 to treat patients with immune thrombocytopenic purpura (ITP). Anti-D IGIV induces extravascular hemolysis, an expected adverse reaction that is consistent with the presumed mechanism of...
journal_title:Blood
pub_type: 杂志文章,评审
doi:
更新日期:2000-04-15 00:00:00
abstract::Although hepatitis C virus (HCV) mainly affects hepatocytes, infection is widespread and involves immunologically privileged sites. Whether lymphoid cells represent further targets of early HCV infection, or whether other cells in the hematopoietic microenvironment may serve as a potential virus reservoir, is still un...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-11-01 00:00:00
abstract::Eighty-three patients with circulating anticoagulants were studied at The New York Hospital. The lupus-type anticoagulant, an inhibitor of the prothrombin activator complex, was demonstrated in 58 patients. The inhibitor was identified using the blood and tissue thromboplastin inhibition tests. Inhibition by the lupus...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1976-10-01 00:00:00
abstract::Factor XIII is the fibrin-stabilizing factor that covalently cross-links fibrin monomers to form a highly organized, stable fibrin clot. The plasma form of factor XIII is a heterodimer, a2b2, consisting of two a-chains and two b-chains; the intracellular form, such as in platelets and placenta, is a dimer, a2, consist...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-08-01 00:00:00
abstract::Immunosuppression resulting in impaired Epstein-Barr virus (EBV)-specific T-cell immunity is involved in the pathogenesis of EBV-positive post-transplantation lymphoproliferative disorder (EBV(+) PTLD). Restoration of EBV-specific T-cell immunity by adoptive immunotherapy can induce remission. EBV-nuclear antigen-1 (E...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-03-274076
更新日期:2010-09-30 00:00:00
abstract::The capacity to convert exogenous leukotriene A4 to lipoxins (LXs) was investigated in platelet suspensions from patients with myeloproliferative disorders (MPD) (n = 22) and healthy control subjects (n = 14). Platelets isolated from the controls produced mainly LXA4, but also 6(S)-LXA4 and the all-trans isomers of li...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-12-01 00:00:00
abstract::Evidence supporting the efficacy of in utero hematopoietic cell transplantation (IUHCT) in a valid large animal model is needed prior to clinical application. The objective of this study was to establish clinically relevant levels of hematopoietic chimerism in a canine model of maternal-to-fetal IUHCT. We first assess...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-11-537571
更新日期:2014-09-18 00:00:00
abstract::The kidney is involved in 70% of patients with immunoglobulin light-chain (AL) amyloidosis, but little is known on progression or reversibility of renal involvement, and criteria for renal response have never been validated. Newly diagnosed patients from the Pavia (n = 461, testing cohort) and Heidelberg (n = 271, val...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-04-570010
更新日期:2014-10-09 00:00:00
abstract::The t(11;14)(q13;q32) translocation, which juxtaposes the BCL1 oncogene with the Ig heavy chain locus, has been associated with an uncommon subtype of non-Hodgkin's lymphoma (NHL) termed mantle cell lymphoma (MCL). To date, no molecular marker that serves as an indicator of tumor progression or clinical prognosis has ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-10-15 00:00:00
abstract::The human leukocyte integrin subunit CD11b is expressed predominantly on myelomonocytic cells. To identify CD11b promoter sequences important for myelomonocytic gene expression and to assess the utility of the CD11b promoter for expressing heterologous genes in vivo, we generated transgenic mice with a human CD4 repor...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-02-15 00:00:00
abstract::Lipid rafts are detergent-resistant, cholesterol- and sphingolipid-rich membrane domains that are involved in important cellular processes such as signal transduction and intracellular trafficking. Stomatin, a major lipid-raft component of erythrocytes and epithelial cells, is also an abundant platelet protein. Micros...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v100.3.897
更新日期:2002-08-01 00:00:00
abstract::In a previous study, we reported that a single injection of cyclophosphamide (CTX) in tumor-bearing mice resulted in tumor eradication when the animals were subsequently injected with tumor-sensitized lymphocytes. Notably, CTX acted by inducing bystander effects on T cells, and the response to the combined CTX/adoptiv...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-03-15 00:00:00
abstract::Burkitt lymphoma (BL) is a highly aggressive B-cell neoplasm harboring chromosomal rearrangements of the c-myc oncogene. BL cells frequently resist apoptosis induction by chemotherapeutic agents; however, the mechanism of unresponsiveness has not been elucidated. Here, we show that cytochrome c fails to stimulate apop...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-10-4075
更新日期:2005-05-15 00:00:00
abstract::Most patients with chronic lymphocytic leukemia (CLL) are diagnosed with early-stage disease and managed with active surveillance. The individual course of patients with early-stage CLL is heterogeneous, and their probability of needing treatment is hardly anticipated at diagnosis. We aimed at developing an internatio...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2019003453
更新日期:2020-05-21 00:00:00
abstract::T cell-based therapies have much promise in cancer treatment. This approach may be enhanced if used in combination with radiotherapy provided that tumor-specific T cells can be protected against the effects of radiotherapy. Previously, we demonstrated that administration of TLR9 ligand into mice decreased activation- ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-07-104141
更新日期:2008-03-01 00:00:00
abstract::This 2-part, double-blind, placebo-controlled study was conducted to determine the safety and efficacy of etoricoxib, a COX-2 selective inhibitor, for the treatment of hemophilic arthropathy. In part 1 (6 weeks), 102 patients (> or = 12 years old) with hemophilic arthropathy were randomized to receive 90 mg etoricoxib...
journal_title:Blood
pub_type: 杂志文章,随机对照试验
doi:10.1182/blood-2004-09-3501
更新日期:2006-03-01 00:00:00
abstract::Lipoxygenases (LXs) catalyze formation of leukotrienes and hydroxy-eicosatetraenoic acids (HETEs), proinflammatory, and spasmogenic autacoids that are critical for host defense systems. We studied the expression and regulation of LX genes (12-LX, 5-LX, and 15-LX) and the 5-lipoxygenase activating protein (FLAP) in hum...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
abstract::Cervical internal carotid artery (cICA) occlusion is a recognized cause of acute ischemic stroke (AIS) in sickle cell disease (SCD), but the associated clinical and radiologic features are not well described. We reviewed data on cervical magnetic resonance angiography (cMRA) performed prospectively in 67 patients (55 ...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2011-03-337915
更新日期:2011-12-01 00:00:00
abstract::Antigens implicated in the graft-versus-leukemia (GVL) effect in chronic myeloid leukemia (CML) include WT1, PR1, and BCR-ABL. To detect very low frequencies of these antigen-specific CD8+ T cells, we used quantitative polymerase chain reaction (qPCR) to measure interferon-gamma (IFN-gamma) mRNA production by peptide-...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-01-0150
更新日期:2003-10-15 00:00:00
abstract::Small cell lung cancer is distinguished from other lung cancer histologic types by possessing a variety of neuroendocrine properties. Anti-Leu-7 is a monoclonal antibody that recognizes a 110,000-dalton molecular weight glycoprotein initially described on natural killer cells and subsequently reported on a variety of ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1985-03-01 00:00:00
abstract::CD20 is a nonglycosylated 33 to 37 kD phosphoprotein involved in B-cell signaling that subserves important functions in the regulation of B-cell proliferation and differentiation. In addition, this B-cell surface antigen has been shown recently to be an effective target for immunotherapy of B-cell malignancies using c...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-03-01 00:00:00
abstract::As B-cell chronic lymphocytic leukemia (B-CLL) progresses, malignant cells extravasate and infiltrate lymphoid tissues. Several molecules, including gelatinase B/MMP-9, contribute to these processes. Although mainly a secreted protease, some MMP-9 is present at the B-CLL cell surface and the function, mode of anchorin...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-08-109249
更新日期:2008-07-01 00:00:00