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Erythropoiesis

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https://www.readbyqxmd.com/read/29349622/transfusion-practice-patterns-in-patients-with-anemia-receiving-myelosuppressive-chemotherapy-for-nonmyeloid-cancer-results-from-a-prospective-observational-study
#1
James Granfortuna, Kaye Shoffner, Stephen E DePasquale, Sejal Badre, Chet Bohac, Cisio De Oliveira Brandao
PURPOSE: The decision to prescribe packed red blood cell (PRBC) transfusions in patients with chemotherapy-induced anemia (CIA) includes assessment of clinical features such as the patient's cancer type and treatment regimen, severity of anemia symptoms, and presence of comorbidities. We examined contemporary transfusion practices in patients with nonmyeloid cancer and CIA. METHODS: Key inclusion criteria were age ≥ 18 years with nonmyeloid cancer, receiving first/second-line myelosuppressive chemotherapy, baseline hemoglobin (Hb) ≤ 10...
January 19, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29340323/clinical-and-pathological-significance-of-autoantibodies-to-erythropoietin-receptor-in-type-2-diabetic-patients-with-ckd
#2
Akinori Hara, Kengo Furuichi, Akihiko Koshino, Haruka Yasuda, Trang Thi Thu Tran, Yasunori Iwata, Norihiko Sakai, Miho Shimizu, Shuichi Kaneko, Hiroyuki Nakamura, Takashi Wada
Introduction: We examined the impact of autoantibodies on the erythropoietin receptor (EPOR) in type 2 diabetic patients with chronic kidney disease (CKD). Methods: A total of 112 Japanese patients with type 2 diabetes who had CKD were enrolled in this study and followed for a mean of 45 months. Sera from these patients were screened for anti-EPOR antibodies using enzyme-linked immunosorbent assays. Results: Anti-EPOR antibodies were detected in 26 patients (23%)...
January 2018: KI Reports
https://www.readbyqxmd.com/read/29339402/canonical-notch-signaling-is-dispensible-for-adult-steady-state-and-stress-myelo-erythropoiesis
#3
Sara Duarte, Petter S Woll, Natalija Buza-Vidas, Desmond Wai Loon Chin, Hanane Boukarabila, Tiago C Luís, Laura Stenson, Tiphaine Bouriez-Jones, Helen Ferry, Adam J Mead, Deborah Atkinson, Shaobo Jin, Sally-Ann Clark, Bishan Wu, Emmanouela Repapi, Nicki Gray, Stephen Taylor, Anders P Mutvei, Yat Long Tsoi, Claus Nerlov, Urban Lendahl, Sten Eirik W Jacobsen
While an essential role for canonical Notch signaling in generation of hematopoietic stem cells in the embryo and in thymic T cell development is well established, its role in adult bone marrow (BM) myelopoiesis remains unclear. Some studies, analyzing myeloid progenitors in adult mice with inhibited Notch signaling, implicated distinct roles of canonical Notch signaling in regulation of progenitors for the megakaryocyte, erythroid and granulocyte-macrophage cell lineages. However, these studies might also have targeted other pathways...
January 16, 2018: Blood
https://www.readbyqxmd.com/read/29336484/epigenetic-regulation-of-megakaryocytic-and-erythroid-differentiation-by-phf2-histone-demethylase
#4
Jichun Yang, Jing Ma, Yu Xiong, Yanlin Wang, Kaiyue Jin, Wenjun Xia, Qing Chen, Jianbo Huang, Jin Zhang, Nan Jiang, Shayi Jiang, Duan Ma
Plant homeodomain finger 2 (PHF2) is a JmjC family histone demethylase that demethylates H3K9me2, a repressive gene marker. PHF2 was found to play a role in the differentiation of several tissue types such as osteoblast and adipocyte differentiation. We report here that PHF2 plays a role in the epigenetic regulation of megakaryocytic (MK) and erythroid differentiation. We investigated PHF2 expression during MK and erythroid differentiation in K562 and human CD34+ progenitor (hCD34+ ) cells. Our data demonstrate that PHF2 expression is down-regulated during megakaryopoiesis and erythropoiesis...
January 16, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29336240/treatment-of-anemia-in-patients-with-solid-tumors-receiving-chemotherapy-in-palliative-setting-usual-practice-versus-guidelines
#5
Robin de Putter, Karen Geboes, Marc De Man, Simon Van Belle
Background Anemia is frequent in patients with cancer and is often multifactorial. Treatment depends on etiology and can consist of transfusions, intravenous iron (IV Fe), and/or erythropoiesis-stimulating agents (ESA). Several studies have shown that cancer-related anemia is undertreated. The aim of this study is to compare usual practice in a university hospital with the international guidelines. Methods Using the hospital and pharmacy informatics all adults (≥18 years), who received a treatment for anemia (transfusion, IV Fe, ESA) from February to August 2016 during palliative chemotherapy, were identified...
January 16, 2018: Acta Clinica Belgica
https://www.readbyqxmd.com/read/29335880/the-long-term-effect-of-erythropoiesis-stimulating-agents-given-to-preterm-infants-a-proton-magnetic-resonance-spectroscopy-study-on-neurometabolites-in-early-childhood
#6
Charles Gasparovic, Arvind Caprihan, Ronald A Yeo, John Phillips, Jean R Lowe, Richard Campbell, Robin K Ohls
BACKGROUND: Erythropoiesis stimulating agents (ESAs) are neuroprotective in cell and animal models of preterm birth. Prematurity has been shown to alter neurometabolite levels in children in studies using proton magnetic resonance spectroscopy (1H-MRS). OBJECTIVE: We hypothesized that ESA treatment in premature infants would tend to normalize neurometabolites by 4-6 years of age. MATERIALS AND METHODS: Children in a longitudinal study of neurodevelopment underwent MRI and 1H-MRS at approximately 4 years and 6 years of age...
January 15, 2018: Pediatric Radiology
https://www.readbyqxmd.com/read/29331635/sotatercept-with-long-term-extension-for-the-treatment-of-anaemia-in-patients-with-lower-risk-myelodysplastic-syndromes-a-phase-2-dose-ranging-trial
#7
Rami Komrokji, Guillermo Garcia-Manero, Lionel Ades, Thomas Prebet, David P Steensma, Joseph G Jurcic, Mikkael A Sekeres, Jesus Berdeja, Michael R Savona, Odile Beyne-Rauzy, Aspasia Stamatoullas, Amy E DeZern, Jacques Delaunay, Gautam Borthakur, Robert Rifkin, Thomas E Boyd, Abderrhamane Laadem, Bond Vo, Jennie Zhang, Marie Puccio-Pick, Kenneth M Attie, Pierre Fenaux, Alan F List
BACKGROUND: Myelodysplastic syndromes are characterised by ineffective erythropoiesis leading to anaemia. Sotatercept (ACE-011) is a novel activin receptor type IIA fusion protein that acts as a ligand trap to neutralise negative regulators of late-stage erythropoiesis. The aim of the study was to establish a safe and effective dose of sotatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes. METHODS: This open-label, multicentre, dose-ranging, phase 2 trial took place at 11 treatment centres in the USA and France...
January 10, 2018: Lancet Haematology
https://www.readbyqxmd.com/read/29330800/evaluation-of-erythrocyte-changes-after-normoxic-return-from-hypoxia
#8
Jihyun Song, Josef T Prchal
Hypoxia increases erythropoiesis by hypoxia-inducible factors (HIF), principally by HIF-2, which upregulates erythropoietin transcription. This results in an increase of red blood cell (RBC) production and delivery of more oxygen to tissues. Upon rapid return to normoxia, hypoxia-induced polycythemia is overcorrected by neocytolysis, a transient destruction of preferentially young RBCs bearing low catalase (downregulated by hypoxia-stimulated microRNA(miR)-21) caused by reactive oxygen species (ROS) from expanded mitochondria...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29329925/phenotypic-and-molecular-characterisation-of-a-serum-free-miniature-erythroid-differentiation-system-suitable-for-high-throughput-screening-and-single-cell-assays
#9
Sachith Mettananda, Kevin Clark, Chris A Fisher, Jackie A Sloane-Stanley, Richard J Gibbons, Douglas R Higgs
In vitro erythroid differentiation systems are used to study the mechanisms underlying normal and abnormal erythropoiesis and to test the effects of various extracellular factors on erythropoiesis. The use of serum or conditioned medium in liquid cultures, and seeding cultures with heterogeneous peripheral blood mononuclear cells confound the reproducibility of these systems. Newer erythroid differentiation culture systems have overcome some of these limitations by using a fully defined, serum-free, medium and initiating cultures using purified CD34+ cells...
January 9, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29329501/sustained-plasma-hepcidin-suppression-and-iron-elevation-by-anticalin-derived-hepcidin-antagonist-in-cynomolgus-monkey
#10
Andreas M Hohlbaum, Hendrik Gille, Stefan Trentmann, Maria Kolodziejczyk, Barbara Rattenstetter, Coby M Laarakkers, Galina Katzmann, Hans Jürgen Christian, Nicole Andersen, Andrea Allersdorfer, Shane A Olwill, Bernd Meibohm, Laurent P Audoly, Dorine W Swinkels, Rachel P L van Swelm
BACKGROUND AND PURPOSE: Anaemia of chronic disease (ACD) has been linked to iron restricted erythropoiesis imposed by high circulating levels of hepcidin, a 25 amino acid hepatocyte-derived peptide that controls systemic iron homeostasis. Here we report the engineering of the human lipocalin-derived, small protein-based Anticalin PRS-080 hepcidin antagonist with high affinity and selectivity. EXPERIMENTAL APPROACH: Anticalin- and hepcidin-specific pharmacokinetic/pharmacodynamic modelling was used to design and select the suitable drug candidate based on half life extension and duration of hepcidin suppression...
January 12, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29322849/safety-profile-of-lenalidomide-in-patients-with-lower-risk-myelodysplastic-syndromes-without-del-5q-results-of-a-phase-3-trial
#11
Antonio Almeida, Pierre Fenaux, Guillermo Garcia-Manero, Stuart L Goldberg, Stefanie Gröpper, Anna Jonasova, Norbert Vey, Carmen Castaneda, Jianhua Zhong, C L Beach, Valeria Santini
The safety profile of lenalidomide use in lower-risk myelodysplastic syndromes (MDS) patients with del(5q) is well-established, but less is known in non-del(5q) patients. We provide safety data from a randomized, phase 3 trial evaluating lenalidomide in 239 patients with lower-risk non-del(5q) MDS ineligible/refractory to erythropoiesis-stimulating agents (ESAs). Compared with placebo, lenalidomide was associated with a higher incidence of grade 3-4 treatment-emergent adverse events (TEAEs; 86% vs. 44%), but not risk of infection (p = ...
January 11, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29321181/mechanisms-of-erythrocyte-development-and-regeneration-implications-for-regenerative-medicine-and-beyond
#12
REVIEW
Emery H Bresnick, Kyle J Hewitt, Charu Mehta, Sunduz Keles, Robert F Paulson, Kirby D Johnson
Hemoglobin-expressing erythrocytes (red blood cells) act as fundamental metabolic regulators by providing oxygen to cells and tissues throughout the body. Whereas the vital requirement for oxygen to support metabolically active cells and tissues is well established, almost nothing is known regarding how erythrocyte development and function impact regeneration. Furthermore, many questions remain unanswered relating to how insults to hematopoietic stem/progenitor cells and erythrocytes can trigger a massive regenerative process termed 'stress erythropoiesis' to produce billions of erythrocytes...
January 10, 2018: Development
https://www.readbyqxmd.com/read/29318218/potential-benefit-associated-with-delaying-initiation-of-hemodialysis-in-a-japanese-cohort
#13
Satoshi Higuchi, Izaya Nakaya, Kazuhiro Yoshikawa, Yoichiro Chikamatsu, Ken-Ei Sada, Suguru Yamamoto, Satoko Takahashi, Hiroyo Sasaki, Jun Soma
Introduction: Late referral to a nephrologist, the type of vascular access, nutritional status, and the estimated glomerular filtration rate (eGFR) at the start of hemodialysis (HD) have been reported as independent risk factors of survival for patients who begin HD. The aim of this study was to clarify the influence of the HD-free interval from the time of an eGFR of 10 ml/min per 1.73 m2 (IGFR10-HD) on patient outcome. Methods: We enrolled 124 patients aged older than 20 years who had HD initiated in a general hospital...
July 2017: KI Reports
https://www.readbyqxmd.com/read/29316681/non-transfusion-dependent-thalassemia-an-update-on-complications-and-management
#14
REVIEW
Joseph Sleiman, Ali Tarhini, Rayan Bou-Fakhredin, Antoine N Saliba, Maria Domenica Cappellini, Ali T Taher
Patients with non-transfusion-dependent thalassemia (NTDT) experience many clinical complications despite their independence from frequent transfusions. Morbidities in NTDT stem from the interaction of multiple pathophysiological factors: ineffective erythropoiesis, iron overload (IOL), and hypercoagulability. Ineffective erythropoiesis and hemolysis are associated with chronic hypoxia and a hypercoagulable state. The latter are linked to a high prevalence of thromboembolic and cerebrovascular events, as well as leg ulcers and pulmonary hypertension...
January 8, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29311459/-low-continuity-rate-of-sucroferric-oxyhydroxide-among-japanese-hemodialysis-patients-with-high-phosphate-binder-pill-burden
#15
Satoru Mitsuboshi, Hitoshi Yamada, Kazuhiko Nagai, Hideo Okajima
 This prospective observational study was conducted to evaluate the continuity, efficacy, and tolerability of sucroferric oxyhydroxide (SO) among hemodialysis (HD) patients who switched to SO from sevelamer hydrochloride (SH) or bixalomer (BX). Participants were 9 HD patients in Kaetsu Hospital who had been receiving more than 9 tablets/d of SH or BX and were switched to SO 750 mg/d. All the participants were men. Over a 6-month observational period, 6 of the 9 patients (67%) discontinued SO because of adverse events, including diarrhea, atheroma, and polycythemia...
2018: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/29303771/short-and-medium-term-biological-variation-estimates-of-red-blood-cell-and-reticulocyte-parameters-in-healthy-subjects
#16
Sabrina Buoro, Anna Carobene, Michela Seghezzi, Barbara Manenti, Paola Dominoni, Aurelio Pacioni, Ferruccio Ceriotti, Cosimo Ottomano, Giuseppe Lippi
BACKGROUND: The integrated evaluation of traditional and innovative red blood cell (RBC) and reticulocyte parameters is a rapid, inexpensive and non-invasive diagnostic tools for differential diagnosis and follow-up of anemia and other pathological conditions needing bone marrow erythropoiesis assessment. Therefore, estimating the biological variation (BV) of these parameters is essential for evaluating the analytical performance of hematological analyzers, and for enabling accurate data interpretation and appropriate clinical management...
January 5, 2018: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29296892/allogeneic-bone-marrow-transplant-in-the-absence-of-cytoreductive-conditioning-rescues-mice-with-%C3%AE-thalassemia-major
#17
Yongliang Huo, Jonathan R Lockhart, Shanrun Liu, Suean Fontenard, Mike Berlett, Thomas M Ryan
β-thalassemia is a group of inherited blood disorders that result in defects in β-globin chain production. Cooley anemia (CA), or β-thalassemia major, is the most severe form of the disease and occurs when an individual has mutations in both copies of the adult β-globin gene. Patients with CA fail to make adult hemoglobin, exhibit ineffective erythropoiesis, experience severe anemia, and are transfusion dependent for life. Currently, allogeneic bone marrow transplantation (BMT) is the only cure; however, few patients have suitable donors for this procedure, which has significant morbidity and mortality...
November 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296795/erythropoiesis-stimulating-agents-in-elderly-patients-with-anemia-response-and-cardiovascular-outcomes
#18
Zachary Gowanlock, Swetha Sriram, Alison Martin, Anargyros Xenocostas, Alejandro Lazo-Langner
A specific cause of anemia cannot be identified in many elderly patients. Erythropoiesis-stimulating agents (ESAs) may play a role in treating these patients with anemia of unknown etiology (AUE). This study examines hemoglobin and cardiovascular outcomes among elderly anemic patients treated with ESAs. We conducted a retrospective cohort study that included all anemic patients older than age 60 years who had erythropoietin (EPO) measured between 2005 and 2013 at a single center. Three independent reviewers used defined criteria to assign each patient's anemia to 1 of 4 groups: chronic kidney disease (CKD), myelodysplastic syndrome, AUE, or other etiology...
August 22, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296759/a-specialized-pathway-for-erythroid-iron-delivery-through-lysosomal-trafficking-of-transferrin-receptor-2
#19
Shadi Khalil, Maja Holy, Stephen Grado, Robert Fleming, Ryo Kurita, Yukio Nakamura, Adam Goldfarb
Erythroid progenitors are the largest consumers of iron in the human body. In these cells, a high flux of iron must reach the mitochondrial matrix to form sufficient heme to support hemoglobinization. Canonical erythroid iron trafficking occurs via the first transferrin receptor (TfR1)-mediated endocytosis of diferric-transferrin into recycling endosomes, where ferric iron is released, reduced, and exported to the cytosol via DMT1. However, mice lacking TfR1 or DMT1 demonstrate residual erythropoiesis, suggesting additional pathways for iron use...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296077/hx575-established-biosimilarity-in-the-treatment-of-renal-anemia-and-10-years-of-clinical-experience
#20
REVIEW
Frank Dellanna, David Goldsmith, Andriy Krendyukov, Andreas Seidl, Nadja Höbel, Christian Combe
Erythropoiesis-stimulating agents, such as recombinant human erythropoietin, are commonly used for the treatment of anemia in patients with chronic kidney disease (CKD). In 2007, HX575 (Binocrit®) became the first biosimilar epoetin alfa to be approved by the European Medicines Agency (EMA). The decision to approve a biosimilar is based on the totality of evidence obtained in a comprehensive comparability exercise that involves extensive analytical characterization, nonclinical studies and clinical studies...
2018: Drug Design, Development and Therapy
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