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https://www.readbyqxmd.com/read/29348121/endothelial-cell-derived-von-willebrand-factor-but-not-platelet-derived-promotes-atherosclerosis-in-apolipoprotein-e-deficient-mice
#1
Prakash Doddapattar, Nirav Dhanesha, Mehul R Chorawala, Chandler Tinsman, Manish Jain, Manasa K Nayak, Janice M Staber, Anil K Chauhan
OBJECTIVE: VWF (von Willebrand factor) is synthesized by endothelial cells and megakaryocytes and is known to contribute to atherosclerosis. In vitro studies suggest that platelet-derived VWF (Plt-VWF) is biochemically and functionally different from endothelial cell-derived VWF (EC-VWF). We determined the role of different pools of VWF in the pathophysiology of atherosclerosis. APPROACH AND RESULTS: Using bone marrow transplantation, we generated chimeric Plt-VWF, EC-VWF, and Plt-VWF mice lacking a disintegrin and metalloprotease with thrombospondin type I repeats-13 in platelets and plasma on apolipoprotein E-deficient (Apoe-/-) background...
January 18, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29342995/-pediatric-myeloid-neoplasms-associated-with-eosinophilia-and-platelet-derived-growth-factor-receptor-beta-gene-rearrangement-a-case-report-and-literature-review
#2
X Y Zhang, T F Liu, C W Li, Q H Li, X F Zhu
Objective: To investigate the clinical features and therapeutic strategies of childhood myeloid neoplasms associated with eosinophilia and platelet-derived growth factor receptor beta (PDGFRB) gene rearrangement. Methods: Clinical data of myeloid neoplasms associated with eosinophilia and t (1;5) (q21;q33) chromosomal translocation of PDGFRB gene rearrangement in a child hospitalized in Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences on May 2015 was collected and analyzed...
January 2, 2018: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/29340130/mechanism-action-of-platelets-and-crucial-blood-coagulation-pathways-in-hemostasis
#3
REVIEW
Mercy Halleluyah Periayah, Ahmad Sukari Halim, Arman Zaharil Mat Saad
Blood is considered to be precious because it is the basic necessity for health; our body needs a steady provision of oxygen, supplied via blood, to reach billions of tissues and cells. Hematopoiesis is the process that generates blood cells of all lineages. However, platelets are the smallest blood component produced from the very large bone marrow cells called megakaryocytes and they play a fundamental role in thrombosis and hemostasis. Platelets contribute their hemostatic capacity via adhesion, activation and aggregation, which are triggered upon tissue injury, and these actions stimulate the coagulation factors and other mediators to achieve hemostasis...
October 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/29339402/canonical-notch-signaling-is-dispensible-for-adult-steady-state-and-stress-myelo-erythropoiesis
#4
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
#5
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/29327715/de-novo-pure-erythroid-leukemia-refining-the-clinicopathologic-and-cytogenetic-characteristics-of-a-rare-entity
#6
Erica F Reinig, Patricia T Greipp, April Chiu, Matthew T Howard, Kaaren K Reichard
Per the revised fourth edition World Health Organization classification of acute myeloid leukemia, pure erythroid leukemia is now the sole type of acute erythroid leukemia. The diagnosis of this rare entity is often challenging and the cytologic overlap with non-neoplastic (eg, megaloblastic anemia) and neoplastic entities (eg, other types of acute leukemia and non-hematopoietic malignancies) warrants a significant degree of clinical, laboratory, immunophenotypic, and genetic investigation. Given the limited number of reports of this rare and diagnostically challenging entity, we report detailed clinicopathologic characteristics from 15 patients, the largest series thus far, of primary de novo pure erythroid leukemia to provide further diagnostic insights into this entity and reveal strategies for making the diagnosis...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29327472/mesenchymal-stem-cell-deficiency-influences-megakaryocytopoiesis-through-the-tnfaip3-nf-%C3%AE%C2%BAb-smad-pathway-in-patients-with-immune-thrombocytopenia
#7
Yun He, Lin-Lin Xu, Fei-Er Feng, Qian-Ming Wang, Xiao-Lu Zhu, Chen-Cong Wang, Jia-Min Zhang, Hai-Xia Fu, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang, Xiao-Hui Zhang
Immune thrombocytopenia (ITP) is an autoimmune disease. Mesenchymal stem cells (MSCs) play important roles in the physiology and homeostasis of the haematopoietic system, including supporting megakaryocytic differentiation from CD34+ haematopoietic progenitor cells. Tumour necrosis factor alpha-induced protein 3 (TNFAIP3, also termed A20) plays a key role in terminating NF-κB signalling. Human genetic studies showed that the polymorphisms of the TNFAIP3 gene may contribute to ITP susceptibility. In this study, we showed a significant decrease in TNFAIP3 and increase in NF-κB/SMAD7 in ITP-MSCs...
January 12, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29326349/notching-down-a-win-for-megakaryocytes
#8
Samir Taoudi
No abstract text is available yet for this article.
January 11, 2018: Blood
https://www.readbyqxmd.com/read/29326119/association-of-mutations-with-morphologic-dysplasia-in-de-novo-acute-myeloid-leukemia-without-2016-who-classification-defined-cytogenetic-abnormalities
#9
Olga K Weinberg, Christopher J Gibson, Traci M Blonquist, Donna Neuberg, Olga Pozdnyakova, Frank Kuo, Benjamin L Ebert, Robert P Hasserjian
Despite improvements in our understanding of the molecular basis of acute myeloid leukemia, the association between genetic mutations with morphologic dysplasia remains unclear. In this study, we evaluated and scored dysplasia in bone marrow specimens from 168 patients with de novo acute myeloid leukemia; none of these patients had 2016 WHO Classification-defined cytogenetic abnormalities. We then performed targeted sequencing of diagnostic bone marrow aspirates for recurrent mutations associated with myeloid malignancies...
January 11, 2018: Haematologica
https://www.readbyqxmd.com/read/29323290/clonal-analysis-of-lineage-fate-in-native-haematopoiesis
#10
Alejo E Rodriguez-Fraticelli, Samuel L Wolock, Caleb S Weinreb, Riccardo Panero, Sachin H Patel, Maja Jankovic, Jianlong Sun, Raffaele A Calogero, Allon M Klein, Fernando D Camargo
Haematopoiesis, the process of mature blood and immune cell production, is functionally organized as a hierarchy, with self-renewing haematopoietic stem cells and multipotent progenitor cells sitting at the very top. Multiple models have been proposed as to what the earliest lineage choices are in these primitive haematopoietic compartments, the cellular intermediates, and the resulting lineage trees that emerge from them. Given that the bulk of studies addressing lineage outcomes have been performed in the context of haematopoietic transplantation, current models of lineage branching are more likely to represent roadmaps of lineage potential than native fate...
January 11, 2018: Nature
https://www.readbyqxmd.com/read/29323256/splicing-of-platelet-resident-pre-mrnas-upon-activation-by-physiological-stimuli-results-in-functionally-relevant-proteome-modifications
#11
Giovanni Nassa, Giorgio Giurato, Giovanni Cimmino, Francesca Rizzo, Maria Ravo, Annamaria Salvati, Tuula A Nyman, Yafeng Zhu, Mattias Vesterlund, Janne Lehtiö, Paolo Golino, Alessandro Weisz, Roberta Tarallo
Platelet activation triggers thrombus formation in physiological and pathological conditions, such as acute coronary syndromes. Current therapies still fail to prevent thrombotic events in numerous patients, indicating that the mechanisms modulating platelet response during activation need to be clarified. The evidence that platelets are capable of de novo protein synthesis in response to stimuli raised the issue of how megakaryocyte-derived mRNAs are regulated in these anucleate cell fragments. Proteogenomics was applied here to investigate this phenomeon in platelets activated in vitro with Collagen or Thrombin Receptor Activating Peptide...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29319374/sensitive-and-specific-assessment-of-recombinant-von-willebrand-factor-in-platelet-function-analyzer
#12
Isabell Pekrul, Thorsten Kragh, Peter L Turecek, Aaron R Novack, Helmut W Ott, Michael Spannagl
BACKGROUND: Recombinant von Willebrand factor (rVWF), which was licensed in the United States in 2015, has the multimeric distribution of freshly secreted VWF with ultralarge (UL) and high molecular weight multimers (HMWM) from endothelial cells and megakaryocytes since it has never been exposed to ADAMTS13 or any other proteolytic enzyme. Measurement of closure time (CT) using the platelet function analyzer-200 (PFA-200) is highly sensitive to the presence of UL VWF multimers in added VWF concentrates...
January 10, 2018: Platelets
https://www.readbyqxmd.com/read/29307747/the-u2af-homology-motif-kinase-1-uhmk1-is-upregulated-upon-hematopoietic-cell-differentiation
#13
Isabella Barbutti, João Agostinho Machado-Neto, Vanessa Cristina Arfelli, Paula de Melo Campos, Fabiola Traina, Sara Teresinha Olalla Saad, Leticia Fröhlich Archangelo
UHMK1 (KIS) is a nuclear serine/threonine kinase that possesses a U2AF homology motif and phosphorylates and regulates the activity of the splicing factors SF1 and SF3b155. Mutations in these components of the spliceosome machinery have been recently implicated in leukemogenesis. The fact that UHMK1 regulates these factors suggests that UHMK1 might be involved in RNA processing and perhaps leukemogenesis. Here we analyzed UHMK1 expression in normal hematopoietic and leukemic cells as well as its function in leukemia cell line...
January 4, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29307605/megakaryocyte-derived-excessive-tgf%C3%AE-1-inhibits-proliferation-of-normal-hematopoietic-stem-cells-in-acute-myeloid-leukemia
#14
Yuemin Gong, Mei Zhao, Wanzhu Yang, Ai Gao, Xiuxiu Yin, Linping Hu, Xiaofang Wang, Jing Xu, Sha Hao, Tao Cheng, Hui Cheng
Impaired production of healthy hematopoietic cells from residual hematopoietic stem cells (HSCs) leads to high mortality in acute myeloid leukemia (AML). Previous studies have identified p21 and Egr3 as intrinsic factors responsible for the growth arrest and differentiation blockade of normal HSCs in leukemia, however, the related extrinsic factors remains unknown. In this study, we demonstrated that TGFβ signaling was up-regulated in HSCs from MLL-AF9 induced AML mice bone marrow, due to excessive production of TGFβ1 especially from megakaryocytes, and over-activation of latent TGFβ1 protein...
January 4, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29301129/amegakaryocytic-thrombocytopenia-and-subsequent-aplastic-anemia-associated-with-apparent-epstein-barr-virus-infection
#15
Ilana Levy, Ruth Laor, Nizar Jiries, Jacob Bejar, Aaron Polliack, Tamar Tadmor
Acquired amegakaryocytic thrombocytopenia (AAT), a rare entity characterized by severe thrombocytopenia and the absence of megakaryocytes in the bone marrow, may mimic or precede the diagnosis of aplastic anemia (AA). Here, we describe a patient who presented with apparent Epstein-Barr virus (EBV)-associated immune thrombocytopenia resistant to several lines of therapies, which was in fact a form of AAT with some features of AA. He eventually responded to therapy with eltrombopag, cyclosporine A (CSA), and antithymocyte globulin (ATG) and recovered completely...
January 5, 2018: Acta Haematologica
https://www.readbyqxmd.com/read/29300724/a-novel-prospective-isolation-of-murine-fetal-liver-progenitors-to-study-in-utero-hematopoietic-defects
#16
Julia E Draper, Patrycja Sroczynska, Muhammad Z H Fadlullah, Rahima Patel, Gillian Newton, Wolfgang Breitwieser, Valerie Kouskoff, Georges Lacaud
In recent years, highly detailed characterization of adult bone marrow (BM) myeloid progenitors has been achieved and, as a result, the impact of somatic defects on different hematopoietic lineage fate decisions can be precisely determined. Fetal liver (FL) hematopoietic progenitor cells (HPCs) are poorly characterized in comparison, potentially hindering the study of the impact of genetic alterations on midgestation hematopoiesis. Numerous disorders, for example infant acute leukemias, have in utero origins and their study would therefore benefit from the ability to isolate highly purified progenitor subsets...
January 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29298288/hierarchically-related-lineage-restricted-fates-of-multipotent-haematopoietic-stem-cells
#17
Joana Carrelha, Yiran Meng, Laura M Kettyle, Tiago C Luis, Ruggiero Norfo, Verónica Alcolea, Francesca Grasso, Adriana Gambardella, Amit Grover, Kari Högstrand, Allegra M Lord, Alejandra Sanjuan-Pla, Petter S Woll, Claus Nerlov, Jacobsen Sten Eirik W
Rare multipotent hematopoietic stem cells (HSCs) in adult bone marrow (BM) with extensive self-renewal potential possess the ability to efficiently replenish all myeloid and lymphoid blood cells1, securing long-term multilineage reconstitution following physiological and clinical challenges, including chemotherapy and hematopoietic transplantations2-4. HSC transplantation remains the only curative treatment for many hematological malignancies, but inefficient blood-lineage replenishment remains a major cause of morbidity and mortality5-6...
January 3, 2018: Nature
https://www.readbyqxmd.com/read/29296963/novel-tpo-receptor-agonist-ta-316-contributes-to-platelet-biogenesis-from-human-ips-cells
#18
Ayako Aihara, Tomo Koike, Natsuki Abe, Sou Nakamura, Akira Sawaguchi, Takanori Nakamura, Naoshi Sugimoto, Hiromitsu Nakauchi, Taito Nishino, Koji Eto
Signaling by thrombopoietin (TPO) in complex with its receptor, c-MPL, is critical for hematopoietic stem cell (HSC) homeostasis and platelet generation. Here we show that TA-316, a novel chemically synthesized c-MPL agonist (CMA), is useful for ex vivo platelet generation from human-induced pluripotent stem (iPS) cell-derived immortalized megakaryocyte progenitor cell lines (imMKCLs). Moreover, the generation is clinically applicable, because self-renewal expansion and platelet release is tightly controllable...
February 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296920/identification-of-a-murine-cd45-f4-80lo-hsc-derived-marrow-endosteal-cell-associated-with-donor-stem-cell-engraftment
#19
Kathleen M Overholt, Satoru Otsuru, Timothy S Olson, Adam J Guess, Victoria M Velazquez, Laura Desbourdes, Massimo Dominici, Edwin M Horwitz
Hematopoietic stem cells (HSCs) reside in specialized microenvironments within the marrow designated as stem cell niches, which function to support HSCs at homeostasis and promote HSC engraftment after radioablation. We previously identified marrow space remodeling after hematopoietic ablation, including osteoblast thickening, osteoblast proliferation, and megakaryocyte migration to the endosteum, which is critical for effective engraftment of donor HSCs. To further evaluate the impact of hematopoietic cells on marrow remodeling, we used a transgenic mouse model (CD45Cre/iDTR) to selectively deplete hematopoietic cells in situ...
December 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296903/osteomacs-interact-with-megakaryocytes-and-osteoblasts-to-regulate-murine-hematopoietic-stem-cell-function
#20
Safa F Mohamad, Linlin Xu, Joydeep Ghosh, Paul J Childress, Irushi Abeysekera, Evan R Himes, Hao Wu, Marta B Alvarez, Korbin M Davis, Alexandra Aguilar-Perez, Jung Min Hong, Angela Bruzzaniti, Melissa A Kacena, Edward F Srour
Networking between hematopoietic stem cells (HSCs) and cells of the hematopoietic niche is critical for stem cell function and maintenance of the stem cell pool. We characterized calvariae-resident osteomacs (OMs) and their interaction with megakaryocytes to sustain HSC function and identified distinguishing properties between OMs and bone marrow (BM)-derived macrophages. OMs, identified as CD45+F4/80+ cells, were easily detectable (3%-5%) in neonatal calvarial cells. Coculture of neonatal calvarial cells with megakaryocytes for 7 days increased OM three- to sixfold, demonstrating that megakaryocytes regulate OM proliferation...
December 12, 2017: Blood Advances
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