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Haematopoietic stem cell

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https://www.readbyqxmd.com/read/28635677/t-cell-manipulation-strategies-to-prevent-graft-versus-host-disease-in-haploidentical-stem-cell-transplantation
#1
REVIEW
Jayakumar Vadakekolathu, Sergio Rutella
Allogeneic haematopoietic stem cell transplantation (HSCT) from an human leukocyte antigen (HLA)-identical donor can be curative for eligible patients with non-malignant and malignant haematological disorders. HSCT from alternative donor sources, such as HLA-mismatched haploidentical donors, is increasingly considered as a viable therapeutic option for patients lacking HLA-matched donors. Initial attempts at haploidentical HSCT were associated with vigorous bidirectional alloreactivity, leading to unacceptably high rates of graft rejection and graft-versus-host disease (GVHD)...
June 21, 2017: Biomedicines
https://www.readbyqxmd.com/read/28634034/absence-of-%C3%AE-chain-in-keratinocytes-alters-chemokine-secretion-resulting-in-reduced-immune-cell-recruitment
#2
Karolin Nowak, Daniela Linzner, Adrian J Thrasher, Paul F Lambert, Wei Li Di, Siobhan O Burns
Loss of function mutations in the common gamma (γc) chain cytokine receptor subunit give rise to severe combined immunodeficiency (SCID) characterised by lack of T and natural killer cells and infant death from infection. Haematopoietic stem cell transplantation or gene therapy offer cure but despite successful replacement of lymphoid immune lineages a long-term risk of severe cutaneous human papilloma virus (HPV) infections persists, possibly related to persistent γc-deficiency in other cell types. Here we demonstrate that keratinocytes, the only cell type directly infected by HPV, express functional γc and its co-receptors...
June 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28631609/autologous-haematopoietic-stem-cell-transplantation-for-systemic-lupus-erythematosus-time-ready-for-a-paradigm-shift
#3
EDITORIAL
Tobias Alexander, Falk Hiepe
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May 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28628276/acute-myeloid-leukaemia-relapsing-after-allogeneic-haematopoietic-stem-cell-transplantation-prognostic-factors-and-impact-of-initial-therapy-of-relapse
#4
Andrew B M Lim, Cameron Curley, Chun Yew Fong, Ian Bilmon, Ashanka Beligaswatte, Duncan Purtill, Bartlomiej Getta, Anne Maree Johnston, Tasman Armytage, Marnie Collins, Kate Mason, Katherine Fielding, Matthew Greenwood, John Gibson, Mark Hertzberg, Matthew Wright, Ian Lewis, John Moore, David Curtis, Jeff Szer, Glen Kennedy, David Ritchie
AIMS: We sought to determine factors associated with overall survival from relapse (OSR) of acute myeloid leukaemia (AML) after allogeneic haematopoietic stem cell transplantation (alloHSCT), and the effect of first salvage therapy and subsequent GVHD on OSR. METHODS: Data on 386 patients from nine Australian centres with relapsed AML post-alloHSCT were collected retrospectively. OSR was calculated using the Kaplan-Meier method. Univariate and multivariate analyses were conducted using the logrank test and proportional hazards modelling respectively, and a prognostic index for OSR was derived from multivariate modelling...
June 19, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28628088/an-individualised-risk-adapted-protocol-of-pre-and-post-transplant-zoledronic-acid-reduces-bone-loss-after-allogeneic-stem-cell-transplantation-results-of-a-phase-ii-prospective-trial
#5
A Grigg, B Butcher, B Khodr, A Bajel, M Hertzberg, S Patil, A B D'Souza, P Ganly, P Ebeling, E Wong
Bone loss occurs frequently following allogeneic haematopoietic stem cell transplantation (alloSCT). The Australasian Leukaemia and Lymphoma Group conducted a prospective phase II study of pretransplant zoledronic acid (ZA) and individualised post-transplant ZA to prevent bone loss in alloSCT recipients. Patients received ZA 4 mg before conditioning. Administration of post-transplant ZA from days 100 to 365 post alloSCT was determined by a risk-adapted algorithm based on serial bone density assessments and glucocorticoid exposure...
June 19, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28626219/base-excision-repair-proteins-couple-activation-induced-cytidine-deaminase-and-endonuclease-g-during-replication-stress-induced-mll-destabilization
#6
B Gole, E Mian, M Rall, L Wiesmüller
The breakpoint cluster region of the MLL gene (MLLbcr) is frequently rearranged in therapy-related and infant acute leukaemia, but the destabilizing mechanism is poorly understood. We recently proposed that DNA replication stress results in MLLbcr cleavage via Endonuclease G (EndoG) and represents the common denominator of genotoxic therapy-induced MLL destabilization. Here we performed a siRNA screen for new factors involved in replication stress-induced MLL rearrangements employing an EGFP-based reporter system...
June 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28623280/ev-3-an-endogenous-human-erythropoietin-isoform-with-distinct-functional-relevance
#7
Christel Bonnas, Liane Wüstefeld, Daniela Winkler, Romy Kronstein-Wiedemann, Ekrem Dere, Katja Specht, Melanie Boxberg, Torsten Tonn, Hannelore Ehrenreich, Herbert Stadler, Inge Sillaber
Generation of multiple mRNAs by alternative splicing is well known in the group of cytokines and has recently been reported for the human erythropoietin (EPO) gene. Here, we focus on the alternatively spliced EPO transcript characterized by deletion of exon 3 (hEPOΔ3). We show co-regulation of EPO and hEPOΔ3 in human diseased tissue. The expression of hEPOΔ3 in various human samples was low under normal conditions, and distinctly increased in pathological states. Concomitant up-regulation of hEPOΔ3 and EPO in response to hypoxic conditions was also observed in HepG2 cell cultures...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28621766/autologous-haematopoietic-stem-cell-transplantation-for-treatment-of-multiple-sclerosis
#8
REVIEW
Paolo A Muraro, Roland Martin, Giovanni Luigi Mancardi, Richard Nicholas, Maria Pia Sormani, Riccardo Saccardi
Autologous haematopoietic stem cell transplantation (AHSCT) is a multistep procedure that enables destruction of the immune system and its reconstitution from haematopoietic stem cells. Originally developed for the treatment of haematological malignancies, the procedure has been adapted for the treatment of severe immune-mediated disorders. Results from ∼20 years of research make a compelling case for selective use of AHSCT in patients with highly active multiple sclerosis (MS), and for controlled trials...
June 16, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28620928/the-importance-of-the-number-of-transplanted-cells-with-dipeptidyl-peptidase-4-expression-on-the-haematopoietic-recovery-and-lymphocyte-reconstitution-in-patients-with-multiple-myeloma-after-autologous-haematopoietic-stem-cell-transplantation
#9
Anna Kopinska, Małgorzata Krawczyk-Kulis, Joanna Dziaczkowska-Suszek, Katarzyna Bieszczad, Krystyna Jagoda, Slawomira Kyrcz-Krzemien
Autologous haematopoietic stem cell transplantation (AHSCT) remains recommended treatment in the first remission in multiple myeloma (MM). In earlier research it has been suggested that there is an influence of the expression of dipeptidyl peptidase-4 (CD26) on both the homing and lymphocyte reconstitution after AHSCT. The aim of the study is to investigate the influence of transplanted cells CD26+ on the haematopoietic recovery and lymphocyte reconstitution after AHSCT in MM. Forty eight patients with MM underwent AHSCT in our centre...
June 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28604763/proline-rich-homeodomain-protein-prh-hhex-is-a-suppressor-of-breast-tumour-growth
#10
R M Kershaw, D Roberts, J Wragg, A M Shaaban, E Humphreys, J Halsall, L Price, R Bicknell, K Gaston, P-S Jayaraman
Breast tumours progress from hyperplasia to ductal carcinoma in situ (DCIS) and invasive breast carcinoma (IBC). PRH/HHEX (proline-rich homeodomain/haematopoietically expressed homeobox) is a transcription factor that displays both tumour suppressor and oncogenic activity in different disease contexts; however, the role of PRH in breast cancer is poorly understood. Here we show that nuclear localization of the PRH protein is decreased in DCIS and IBC compared with normal breast. Our previous work has shown that PRH phosphorylation by protein kinase CK2 prevents PRH from binding to DNA and regulating the transcription of multiple genes encoding growth factors and growth factor receptors...
June 12, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28604734/adult-haematopoietic-stem-cell-niches
#11
REVIEW
Genevieve M Crane, Elise Jeffery, Sean J Morrison
Stem cell niches are specialized microenvironments that promote the maintenance of stem cells and regulate their function. Recent advances have improved our understanding of the niches that maintain adult haematopoietic stem cells (HSCs). These advances include new markers for HSCs and niche cells, systematic analyses of the expression patterns of niche factors, genetic tools for functionally identifying niche cells in vivo, and improved imaging techniques. Together, they have shown that HSC niches are perivascular in the bone marrow and spleen...
June 12, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28595566/a-systemic-review-of-the-sources-of-adult-mesenchymal-stem-cells-and-their-suitability-in-musculoskeletal-applications
#12
Rhiannon Nancarrow-Lei, Pouya Mafi, Reza Mafi, Wasim Khan
Background: Adult mesenchymal stem cells (MSCs) were first isolated from bone marrow by Friedenstein in 1976. These cells were clonogenic, non-haematopoietic, and able to replicate extensively in vitro. The fields of regenerative medicine and tissue engineering have grown dramatically since their inception. In the decades since, MSCs have been identified from mesoderm-, endoderm- and ectoderm-derived tissues. In light of our ageing population, the need for effective cell-based therapies for tissue repair and regeneration is ever-expanding...
June 8, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28593997/severe-congenital-neutropenias
#13
REVIEW
Julia Skokowa, David C Dale, Ivo P Touw, Cornelia Zeidler, Karl Welte
Severe congenital neutropenias are a heterogeneous group of rare haematological diseases characterized by impaired maturation of neutrophil granulocytes. Patients with severe congenital neutropenia are prone to recurrent, often life-threatening infections beginning in their first months of life. The most frequent pathogenic defects are autosomal dominant mutations in ELANE, which encodes neutrophil elastase, and autosomal recessive mutations in HAX1, whose product contributes to the activation of the granulocyte colony-stimulating factor (G-CSF) signalling pathway...
June 8, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28593990/loss-of-asxl2-leads-to-myeloid-malignancies-in-mice
#14
Jianping Li, Fuhong He, Peng Zhang, Shi Chen, Hui Shi, Yanling Sun, Ying Guo, Hui Yang, Na Man, Sarah Greenblatt, Zhaomin Li, Zhengyu Guo, Yuan Zhou, Lan Wang, Lluis Morey, Sion Williams, Xi Chen, Qun-Tian Wang, Stephen D Nimer, Peng Yu, Qian-Fei Wang, Mingjiang Xu, Feng-Chun Yang
ASXL2 is frequently mutated in acute myeloid leukaemia patients with t(8;21). However, the roles of ASXL2 in normal haematopoiesis and the pathogenesis of myeloid malignancies remain unknown. Here we show that deletion of Asxl2 in mice leads to the development of myelodysplastic syndrome (MDS)-like disease. Asxl2(-/-) mice have an increased bone marrow (BM) long-term haematopoietic stem cells (HSCs) and granulocyte-macrophage progenitors compared with wild-type controls. Recipients transplanted with Asxl2(-/-) and Asxl2(+/-) BM cells have shortened lifespan due to the development of MDS-like disease or myeloid leukaemia...
June 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28589551/centre-characteristics-and-procedure-related-factors-have-an-impact-on-outcomes-of-allogeneic-transplantation-for-patients-with-cll-a-retrospective-analysis-from-the-european-society-for-blood-and-marrow-transplantation-ebmt
#15
Johannes Schetelig, Liesbeth C de Wreede, Niels S Andersen, Carol Moreno, Michel van Gelder, Antonin Vitek, Michal Karas, Mauricette Michallet, Maciej Machaczka, Martin Gramatzki, Dietrich Beelen, Jürgen Finke, Julio Delgado, Liisa Volin, Jakob Passweg, Peter Dreger, Nicolaas Schaap, Eva Wagner, Anja Henseler, Anja van Biezen, Martin Bornhäuser, Simona Iacobelli, Hein Putter, Stefan O Schönland, Nicolaus Kröger
The best approach for allogeneic haematopoietic stem cell transplantations (alloHCT) in patients with chronic lymphocytic leukaemia (CLL) is unknown. We therefore analysed the impact of procedure- and centre-related factors on 5-year event-free survival (EFS) in a large retrospective study. Data of 684 CLL patients who received a first alloHCT between 2000 and 2011 were analysed by multivariable Cox proportional hazards models with a frailty component to investigate unexplained centre heterogeneity. Five-year EFS of the whole cohort was 37% (95% confidence interval [CI], 34-42%)...
June 7, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28579852/treatment-of-myelofibrosis-old-and-new-strategies
#16
REVIEW
Alessandra Iurlo, Daniele Cattaneo
Myelofibrosis (MF) is a BCR-ABL1-negative myeloproliferative neoplasm that is mainly characterised by reactive bone marrow fibrosis, extramedullary haematopoiesis, anaemia, hepatosplenomegaly, constitutional symptoms, leukaemic progression, and shortened survival. As such, this malignancy is still orphan of curative treatments; indeed, the only treatment that has a clearly demonstrated impact on disease progression is allogeneic haematopoietic stem cell transplantation, but only a minority of patients are eligible for such intensive therapy...
2017: Clinical Medicine Insights. Blood Disorders
https://www.readbyqxmd.com/read/28574591/bone-marrow-adipocytes-support-haematopoietic-stem-cell-survival
#17
Domenico Mattiucci, Giulia Maurizi, Valerio Izzi, Lorenzo Cenci, Marco Ciarlantini, Stefania Mancini, Emanuela Mensà, Raffaele Pascarella, Marco Vivarelli, Attilio Olivieri, Pietro Leoni, Antonella Poloni
In bone marrow (BM), haematopoietic elements are mingled with adipocytes (BM-A), which are the most abundant stromal component in the niche. BM-A progressively increase with ageing, eventually occupying up to 50% of BM cavities. In this work, the role played by BM-A was explored by studying primary human BM-A isolated from hip surgery patients at the molecular level, through microarray analysis, and at the functional level, by assessing their relationship with primary human haematopoietic stem cells (HSC) by the long-term culture initiating cell (LTC-IC) assay...
June 2, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28570710/pmrunt-regulated-by-pm-mir-183-participates-in-nacre-formation-possibly-through-promoting-the-expression-of-collagen-vi-like-and-nacrein-in-pearl-oyster-pinctada-martensii
#18
Zhe Zheng, Xiaodong Du, Xinwei Xiong, Yu Jiao, Yuewen Deng, Qingheng Wang, Ronglian Huang
Heterodimeric PEBP2/CBFs are key regulators in diverse biological processes, such as haematopoietic stem-cell generation, bone formation and cancers. In this work, we cloned runt-like transcriptional factor (designated as PmRunt) and CBF β (designated as PmCBF) gene, which comprise the heterodimeric transcriptional factor in Pinctada martensii. PmRunt was identified with an open reading frame that encodes 545 amino acids and has typical Runt domain. Phylogenetic analysis results speculated that runt-like transcriptional factors (RDs) in vertebrates and invertebrates are separated into two branches...
2017: PloS One
https://www.readbyqxmd.com/read/28561053/mitochondria-link-metabolism-and-epigenetics-in-haematopoiesis
#19
John C Schell, Jared Rutter
Due to their varied metabolic and signalling roles, mitochondria are important in mediating cell behaviour. By altering mitochondrial function, two studies now identify metabolite-induced epigenetic changes that have profound effects on haematopoietic stem cell fate and function.
May 31, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28560469/gene-therapy-for-lysosomal-storage-disorders-recent-advances-for-metachromatic-leukodystrophy-and-mucopolysaccaridosis-i
#20
REVIEW
Rachele Penati, Francesca Fumagalli, Valeria Calbi, Maria Ester Bernardo, Alessandro Aiuti
Lysosomal storage diseases (LSDs) are rare inherited metabolic disorders characterized by a dysfunction in lysosomes, leading to waste material accumulation and severe organ damage. Enzyme replacement therapy (ERT) and haematopoietic stem cell transplant (HSCT) have been exploited as potential treatments for LSDs but pre-clinical and clinical studies have shown in some cases limited efficacy. Intravenous ERT is able to control the damage of visceral organs but cannot prevent nervous impairment. Depending on the disease type, HSCT has important limitations when performed for early variants, unless treatment occurs before disease onset...
May 30, 2017: Journal of Inherited Metabolic Disease
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