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Haematopoiesis

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https://www.readbyqxmd.com/read/28000664/endothelial-specific-inhibition-of-nf-%C3%AE%C2%BAb-enhances-functional-haematopoiesis
#1
Michael G Poulos, Pradeep Ramalingam, Michael C Gutkin, Maria Kleppe, Michael Ginsberg, Michael J P Crowley, Olivier Elemento, Ross L Levine, Shahin Rafii, Jan Kitajewski, Matthew B Greenblatt, Jae-Hyuck Shim, Jason M Butler
Haematopoietic stem cells (HSCs) reside in distinct niches within the bone marrow (BM) microenvironment, comprised of endothelial cells (ECs) and tightly associated perivascular constituents that regulate haematopoiesis through the expression of paracrine factors. Here we report that the canonical NF-κB pathway in the BM vascular niche is a critical signalling axis that regulates HSC function at steady state and following myelosuppressive insult, in which inhibition of EC NF-κB promotes improved HSC function and pan-haematopoietic recovery...
December 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27941891/haematopoiesis-hsc-function-determined-by-epigenetic-memory
#2
Kirsty Minton
No abstract text is available yet for this article.
January 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/27932297/dynamic-self-organisation-of-haematopoiesis-and-a-symmetric-cell-division
#3
Marthe Måløy, Frode Måløy, Per Jakobsen, Bjørn Olav Brandsdal
A model of haematopoiesis that links self-organisation with symmetric and asymmetric cell division is presented in this paper. It is assumed that all cell divisions are completely random events, and that the daughter cells resulting from symmetric and asymmetric stem cell divisions are, in general, phenotypically identical, and still, the haematopoietic system has the flexibility to self-renew, produce mature cells by differentiation, and regenerate undifferentiated and differentiated cells when necessary, due to self-organisation...
December 5, 2016: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/27895715/protein-kinase-msk1-physically-and-functionally-interacts-with-the-kmt2a-mll1-methyltransferase-complex-and-contributes-to-the-regulation-of-multiple-target-genes
#4
Maaike Wiersma, Marianne Bussiere, John A Halsall, Nil Turan, Robert Slany, Bryan M Turner, Karl P Nightingale
BACKGROUND: The KMT2A/MLL1 lysine methyltransferase complex is an epigenetic regulator of selected developmental genes, in part through the SET domain-catalysed methylation of H3K4. It is essential for normal embryonic development and haematopoiesis and frequently mutated in cancer. The catalytic properties and targeting of KMT2A/MLL1 depend on the proteins with which it complexes and the post-translational protein modifications which some of these proteins put in place, though detailed mechanisms remain unclear...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27881874/acute-myeloid-leukemia-derived-from-lympho-myeloid-clonal-hematopoiesis
#5
F Thol, S Klesse, L Köhler, R Gabdoulline, A Kloos, A Liebich, M Wichmann, A Chaturvedi, J Fabisch, V I Gaidzik, P Paschka, L Bullinger, G Bug, H Serve, G Göhring, B Schlegelberger, M Lübbert, H Kirchner, M Wattad, D Kraemer, B Hertenstein, G Heil, W Fiedler, J Krauter, R F Schlenk, K Döhner, H Döhner, A Ganser, M Heuser
We studied acute myeloid leukemia (AML) patients with lympho-myeloid clonal hematopoiesis (LM-CH), defined by the presence of DNA methyltransferase 3A (DNMT3A) mutations in both the myeloid and lymphoid T-cell compartment. Diagnostic, complete remission (CR) and relapse samples were sequenced for 34 leukemia-related genes in 171 DNMT3A mutated adult AML patients. AML with LM-CH was found in 40 patients (23%) and was associated with clonal hematopoiesis of indeterminate potential years before AML, older age, secondary AML and more frequent MDS-type co-mutations (TET2, RUNX1 and EZH2)...
January 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27876786/a-view-of-human-haematopoietic-development-from-the-petri-dish
#6
Andrea Ditadi, Christopher M Sturgeon, Gordon Keller
Human pluripotent stem cells (hPSCs) provide an unparalleled opportunity to establish in vitro differentiation models that will transform our approach to the study of human development. In the case of the blood system, these models will enable investigation of the earliest stages of human embryonic haematopoiesis that was previously not possible. In addition, they will provide platforms for studying the origins of human blood cell diseases and for generating de novo haematopoietic stem and progenitor cell populations for cell-based regenerative therapies...
January 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/27870830/clonal-fate-mapping-quantifies-the-number-of%C3%A2-haematopoietic-stem-cells-that-arise-during%C3%A2-development
#7
Jonathan Henninger, Buyung Santoso, Stefan Hans, Ellen Durand, Jessica Moore, Christian Mosimann, Michael Brand, David Traver, Leonard Zon
Haematopoietic stem cells (HSCs) arise in the developing aorta during embryogenesis. The number of HSC clones born has been estimated through transplantation, but experimental approaches to assess the absolute number of forming HSCs in a native setting have remained challenging. Here, we applied single-cell and clonal analysis of HSCs in zebrafish to quantify developing HSCs. Targeting creER(T2) in developing cd41:eGFP(+) HSCs enabled long-term assessment of their blood contribution. We also applied the Brainbow-based multicolour Zebrabow system with drl:creER(T2) that is active in early haematopoiesis to induce heritable colour barcoding unique to each HSC and its progeny...
January 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/27858992/sox12-a-novel-potential-target-for-acute-myeloid-leukaemia
#8
Haixia Wan, Jiayi Cai, Fangyuan Chen, Jianyi Zhu, Jihua Zhong, Hua Zhong
The role of SRY-related high-mobility-group box (SOX) 12 in leukaemia progression and haematopoiesis remains elusive. This study aimed to examine the expression and function of SOX12 in acute myeloid leukaemia (AML) using human myeloid leukaemia samples and the acute myeloid cell line THP1. Mononuclear cells were isolated from the bone marrow of AML patients and healthy donors. SOX12 expression in haematopoietic cells was evaluated by reverse transcription polymerase chain reaction (RT-PCR). SOX12 short hairpin RNAs (shRNAs) were transduced into THP1 cells, and gene knockdown was confirmed by quantitative RT-PCR and Western blot analysis...
November 18, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27836923/single-nucleotide-polymorphism-array-snp-a-improves-the-identification-of-chromosomal-abnormalities-by-metaphase-cytogenetics-in-myelodysplastic-syndrome
#9
Fernanda Borges da Silva, João Agostinho Machado-Neto, Virginia Helena Leira Lipoli Bertini, Elvira Deolinda Rodrigues Pereira Velloso, Cristina Alonso Ratis, Rodrigo T Calado, Belinda Pinto Simões, Eduardo Magalhães Rego, Fabiola Traina
AIMS: The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal haematopoietic stem cell disorders characterised by inefficient haematopoiesis and risk of progression to acute myeloid leukaemia. Metaphase cytogenetics is an extremely valuable clinical tool in the management of haematological malignancies. However, metaphase cytogenetics requires cellular proliferation, its sensitivity and resolution depends on the proportion of clonal cells in the sample and size of the lesion, respectively...
November 11, 2016: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/27834397/the-genetics-of-myelodysplastic-syndrome-from-clonal-haematopoiesis-to-secondary-leukaemia
#10
Adam S Sperling, Christopher J Gibson, Benjamin L Ebert
Myelodysplastic syndrome (MDS) is a clonal disease that arises from the expansion of mutated haematopoietic stem cells. In a spectrum of myeloid disorders ranging from clonal haematopoiesis of indeterminate potential (CHIP) to secondary acute myeloid leukaemia (sAML), MDS is distinguished by the presence of peripheral blood cytopenias, dysplastic haematopoietic differentiation and the absence of features that define acute leukaemia. More than 50 recurrently mutated genes are involved in the pathogenesis of MDS, including genes that encode proteins involved in pre-mRNA splicing, epigenetic regulation and transcription...
January 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/27817226/-quo-vadis-hematology
#11
Zsolt Matula, Gyöngyi Kudlik, Veronika Urbán S, Ferenc Uher
For decades, developing hematopoietic cells have been strictly compartmentalized into a small population of multipotent self-renewing hematopoietic stem cells, multipotent hematopoietic progenitor cells that are undergoing commitment to myeloid or lymphoid fates, and unipotent precursor cells that mature towards peripheral blood and immune cells. Recent studies, however, have provided a battery of findings that cannot be explained by this "classical" hierarchical model for the architecture of hematopoiesis...
November 2016: Orvosi Hetilap
https://www.readbyqxmd.com/read/27786336/the-hippo-pathway-regulates-human-megakaryocytic-differentiation
#12
Chanchao Lorthongpanich, Nittaya Jiamvoraphong, Kantpitchar Supraditaporn, Phatchanat Klaihmon, Yaowalak U-Pratya, Surapol Issaragrisil
The Hippo pathway is involved in several biological processes in both flies and mammals. Recent studies have shown that the Hippo pathway regulates Drosophila's haematopoiesis; however, understanding of its role in mammalian haematopoiesis is still limited. In flies, deletion of the Hippo component gene, Warts, affects crystal cell differentiation. We explored the role of the Hippo pathway in human haematopoiesis focusing on megakaryopoiesis. To investigate the role of LATS1/2 (a mammalian homolog of Warts) in human megakaryoblastic cell differentiation and platelet formation, megakaryoblastic cell (MEG-01) line was used as a model to gain insight into mechanism of the Hippo pathway in mammalian megakaryopoiesis...
October 27, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27764999/a-fatal-case-of-transplantation-mediated-alloimmune-thrombocytopenia-following-liver-transplantation
#13
Q A Hill, L C Harrison, A D Padmakumar, R G Owen, K R Prasad, G F Lucas, P Tachtatzis
OBJECTIVE AND IMPORTANCE: Transplantation-mediated alloimmune thrombocytopenia (TMAT) occurs when leukocytes transferred in a donor organ from a patient with immune thrombocytopenia (ITP), mount a response against recipient platelets. We present the first fatal case of TMAT following liver transplantation and review its aetiology and treatment. CLINICAL PRESENTATION: The liver donor had ITP and died from an intracranial haemorrhage. The recipient platelet count fell to 2 × 10(9)/l on post-operative day 2...
October 21, 2016: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/27762266/semi-automated-closed-system-manufacturing-of-lentivirus-gene-modified-haematopoietic-stem-cells-for-gene-therapy
#14
Jennifer E Adair, Timothy Waters, Kevin G Haworth, Sara P Kubek, Grant D Trobridge, Jonah D Hocum, Shelly Heimfeld, Hans-Peter Kiem
Haematopoietic stem cell (HSC) gene therapy has demonstrated potential to treat many diseases. However, current state of the art requires sophisticated ex vivo gene transfer in a dedicated Good Manufacturing Practices facility, limiting availability. An automated process would improve the availability and standardized manufacture of HSC gene therapy. Here, we develop a novel program for semi-automated cell isolation and culture equipment to permit complete benchtop generation of gene-modified CD34(+) blood cell products for transplantation...
October 20, 2016: Nature Communications
https://www.readbyqxmd.com/read/27725143/analysis-of-hematopathology-and-alteration-of-jak1-stat3-stat5-signaling-axis-in-experimental-myelodysplastic-syndrome
#15
Suchismita Daw, Ritam Chatterjee, Aditya Law, Sujata Law
Hematological disorders like myelodysplastic syndrome (MDS) may arise due to cumulative dysregulation of various signalling pathways controlling proliferation, differentiation, maturation and apoptosis of bone marrow cells. This devastating bone marrow condition can be due to consequential abnormalities in haematopoiesis as well as its supportive microenvironment. Although mutations related to JAK/STAT pathway are common in myeloproliferative neoplasms, further studies are required to fully explore the myelodysplastic scenario regarding the concerned pathway...
December 25, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27713415/endoglin-integrates-bmp-and-wnt-signalling-to-induce-haematopoiesis-through-jdp2
#16
June Baik, Alessandro Magli, Naoyuki Tahara, Scott A Swanson, Naoko Koyano-Nakagawa, Luciene Borges, Ron Stewart, Daniel J Garry, Yasuhiko Kawakami, James A Thomson, Rita C R Perlingeiro
Mechanisms of haematopoietic and cardiac patterning remain poorly understood. Here we show that the BMP and Wnt signalling pathways are integrated in an endoglin (Eng)-dependent manner in cardiac and haematopoietic lineage specification. Eng is expressed in early mesoderm and marks both haematopoietic and cardiac progenitors. In the absence of Eng, yolk sacs inappropriately express the cardiac marker, Nkx2.5. Conversely, high levels of Eng in vitro and in vivo increase haematopoiesis and inhibit cardiogenesis...
October 7, 2016: Nature Communications
https://www.readbyqxmd.com/read/27671750/concise-review-stem-cell-population-biology-insights-from-hematopoiesis
#17
REVIEW
Adam L MacLean, Cristina Lo Celso, Michael P H Stumpf
Stem cells are fundamental to human life and offer great therapeutic potential, yet their biology remains incompletely-or in cases even poorly-understood. The field of stem cell biology has grown substantially in recent years due to a combination of experimental and theoretical contributions: the experimental branch of this work provides data in an ever-increasing number of dimensions, while the theoretical branch seeks to determine suitable models of the fundamental stem cell processes that these data describe...
January 2017: Stem Cells
https://www.readbyqxmd.com/read/27614454/cryopreserved-nk-cells-in-the-treatment-of-haematological-malignancies-preclinical-study
#18
Monika Holubova, Michaela Miklikova, Martin Leba, Daniel Georgiev, Pavel Jindra, Martin Caprnda, Rachele Ciccocioppo, Peter Kruzliak, Daniel Lysak
BACKGROUND: Leukaemia is an aggressive cancer of haematopoiesis. Despite increasing treatment success, the relapse rate is still high. Natural killer (NK) cells play a key role in the immune response to malignancies; thus, it is conceivable that NK cell-based immunotherapy may control relapses, while extending the disease-free survival. In our study, we investigated whether cryopreserved NK cells are able to kill the leukaemic K562 cell line, the necessity of IL-2 co-application and the association of activation marker expression (NKp44, NKG2D and CD25) with cytotoxic potential...
December 2016: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/27604872/a-quantitative-proteomics-approach-identifies-etv6-and-ikzf1-as-new-regulators-of-an-erg-driven-transcriptional-network
#19
Ashwin Unnikrishnan, Yi F Guan, Yizhou Huang, Dominik Beck, Julie A I Thoms, Sofie Peirs, Kathy Knezevic, Shiyong Ma, Inge V de Walle, Ineke de Jong, Zara Ali, Ling Zhong, Mark J Raftery, Tom Taghon, Jonas Larsson, Karen L MacKenzie, Pieter Van Vlierberghe, Jason W H Wong, John E Pimanda
Aberrant stem cell-like gene regulatory networks are a feature of leukaemogenesis. The ETS-related gene (ERG), an important regulator of normal haematopoiesis, is also highly expressed in T-ALL and acute myeloid leukaemia (AML). However, the transcriptional regulation of ERG in leukaemic cells remains poorly understood. In order to discover transcriptional regulators of ERG, we employed a quantitative mass spectrometry-based method to identify factors binding the 321 bp ERG +85 stem cell enhancer region in MOLT-4 T-ALL and KG-1 AML cells...
December 15, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27546487/clonal-haematopoiesis-harbouring-aml-associated-mutations-is-ubiquitous-in-healthy-adults
#20
Andrew L Young, Grant A Challen, Brenda M Birmann, Todd E Druley
Clonal haematopoiesis is thought to be a rare condition that increases in frequency with age and predisposes individuals to haematological malignancy. Recent studies, utilizing next-generation sequencing (NGS), observed haematopoietic clones in 10% of 70-year olds and rarely in younger individuals. However, these studies could only detect common haematopoietic clones->0.02 variant allele fraction (VAF)-due to the error rate of NGS. To identify and characterize clonal mutations below this threshold, here we develop methods for targeted error-corrected sequencing, which enable the accurate detection of clonal mutations as rare as 0...
2016: Nature Communications
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