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Megakaryocyte

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https://www.readbyqxmd.com/read/29792844/bizarre-multilobated-myeloma-cells-mimicking-megakaryocytes
#1
Sunil Pasricha, Neha Singh, Ajit Panaych, Anurag Mehta
No abstract text is available yet for this article.
May 19, 2018: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/29787432/pegylated-il-11-bbt-059-a-novel-radiation-countermeasure-for-hematopoietic-acute-radiation-syndrome
#2
Vidya P Kumar, Shukla Biswas, Neel K Sharma, Sasha Stone, Christine M Fam, George N Cox, Sanchita P Ghosh
Interleukin-11 was developed to reduce chemotherapy-induced thrombocytopenia; however, its clinical use was limited by severe adverse effects in humans. PEGylated interleukin-11 (BBT-059), developed by Bolder Biotechnology, Inc., exhibited a longer half-life in rodents and induced longer-lasting increases in hematopoietic cells than interleukin-11. A single dose of 1.2 mg kg of BBT-059, administered subcutaneously to CD2F1 mice (12-14 wk, male) was found to be safe in a 14 d toxicity study. The drug demonstrated its efficacy both as a prophylactic countermeasure and a mitigator in CD2F1 mice exposed to Co gamma total-body irradiation...
July 2018: Health Physics
https://www.readbyqxmd.com/read/29787328/megakaryocyte-apoptosis-in-immune-thrombocytopenia
#3
John R Vrbensky, Ishac Nazy, Lisa J Toltl, Catherine Ross, Nikola Ivetic, James W Smith, John G Kelton, Donald M Arnold
The mechanisms of platelet underproduction in immune thrombocytopenia (ITP) remain unknown. While the number of megakaryocytes is normal or increased in ITP bone marrow, further studies of megakaryocyte integrity are needed. Megakaryocytes are responsible for the production of platelets in the bone marrow, and they are possible targets of immune-mediated injury in ITP. Since the biological process of megakaryocyte apoptosis impacts platelet production, we investigated megakaryocyte DNA fragmentation as a marker of apoptosis from ITP bone marrow biopsies...
May 22, 2018: Platelets
https://www.readbyqxmd.com/read/29786092/mapping-the-physical-network-of-cellular-interactions
#4
Jean-Charles Boisset, Judith Vivié, Dominic Grün, Mauro J Muraro, Anna Lyubimova, Alexander van Oudenaarden
A cell's function is influenced by the environment, or niche, in which it resides. Studies of niches usually require assumptions about the cell types present, which impedes the discovery of new cell types or interactions. Here we describe ProximID, an approach for building a cellular network based on physical cell interaction and single-cell mRNA sequencing, and show that it can be used to discover new preferential cellular interactions without prior knowledge of component cell types. ProximID found specific interactions between megakaryocytes and mature neutrophils and between plasma cells and myeloblasts and/or promyelocytes (precursors of neutrophils) in mouse bone marrow, and it identified a Tac1+ enteroendocrine cell-Lgr5+ stem cell interaction in small intestine crypts...
May 21, 2018: Nature Methods
https://www.readbyqxmd.com/read/29783667/bone-marrow-defects-and-platelet-function-a-focus-on-mds-and-cll
#5
REVIEW
Sarah Luu, Elizabeth E Gardiner, Robert K Andrews
The bloodstream typically contains >500 billion anucleate circulating platelets, derived from megakaryocytes in the bone marrow. This review will focus on two interesting aspects of bone marrow dysfunction and how this impacts on the quality of circulating platelets. In this regard, although megakaryocytes are from the myeloid lineage leading to granulocytes (including neutrophils), erythrocytes, and megakaryocytes/platelets, recent evidence has shown that defects in the lymphoid lineage leading to B cells, T cells, and natural killer (NK) cells also result in abnormal circulating platelets...
May 18, 2018: Cancers
https://www.readbyqxmd.com/read/29777586/platelets-autotaxin-and-lysophosphatidic-acid-signaling-win-win-factors-for-cancer-metastasis
#6
REVIEW
Raphael Leblanc, Audrey Houssin, Olivier Peyruchaud
Platelets play a crucial role in the survival of metastatic cells in the blood circulation. Interaction of tumor cells with platelets leads to the production of plethoric factors among which our review will focus on lysophosphatidic acid (LPA) because platelets are the highest producers of this bioactive lysophospholipid in the organism. LPA promotes platelet aggregation and blocking platelet function leads to inhibition of breast cancer cell metastasis through decreased LPA signaling. Autotaxin (ATX), a lysophospholipase D responsible for basal concentration of LPA in blood, was detected in platelet α-granules...
May 19, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29773597/hematopoietic-stem-cell-loss-and-hematopoietic-failure-in-severe-aplastic-anemia-is-driven-by-macrophages-and-aberrant-podoplanin-expression
#7
Amanda McCabe, Julianne N P Smith, Angelica Costello, Jackson Maloney, Divya Katikaneni, Katherine C MacNamara
Severe aplastic anemia results from profound hematopoietic stem cell loss. T cells and interferon gamma have long been associated with severe aplastic anemia, yet the underlying mechanisms driving hematopoietic stem cell loss remain unknown. Using a mouse model of severe aplastic anemia, we demonstrate that interferon gamma-dependent hematopoietic stem cell loss required macrophages. Interferon gamma was necessary for bone marrow macrophage persistence, despite loss of other myeloid cells and hematopoietic stem cells...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29767839/jak2-v617f-positive-acute-myeloid-leukaemia-aml-a-comparison-between-de-novo-aml-and-secondary-aml-transformed-from-an-underlying-myeloproliferative-neoplasm-a-study-from-the-bone-marrow-pathology-group
#8
Jason Aynardi, Rashmi Manur, Paul R Hess, Seble Chekol, Jennifer J D Morrissette, Daria Babushok, Elizabeth Hexner, Heesun J Rogers, Eric D Hsi, Elizabeth Margolskee, Attilio Orazi, Robert Hasserjian, Adam Bagg
The JAK2 V617F mutation is characteristic of most Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) and occurs rarely in de novo acute myeloid leukaemia (AML). We sought to characterize AMLs that harbour this mutation and distinguish those that arise de novo (AML-DN) from those that reflect transformation of an underlying MPN (AML-MPN). Forty-five patients with JAK2 V617F-mutated AML were identified; 15 were AML-DN and 30 were AML-MPN. AML-MPN cases were more likely to have splenomegaly (P = 0·02), MPN-like megakaryocytes and higher mean JAK2 V617F VAF at diagnosis (P = 0·04)...
May 16, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29765026/hematopoietic-stem-cells-can-differentiate-into-restricted-myeloid-progenitors-before-cell-division-in-mice
#9
Tatyana Grinenko, Anne Eugster, Lars Thielecke, Beáta Ramasz, Anja Krüger, Sevina Dietz, Ingmar Glauche, Alexander Gerbaulet, Malte von Bonin, Onur Basak, Hans Clevers, Triantafyllos Chavakis, Ben Wielockx
Hematopoietic stem cells (HSCs) continuously replenish all blood cell types through a series of differentiation steps and repeated cell divisions that involve the generation of lineage-committed progenitors. However, whether cell division in HSCs precedes differentiation is unclear. To this end, we used an HSC cell-tracing approach and Ki67RFP knock-in mice, in a non-conditioned transplantation model, to assess divisional history, cell cycle progression, and differentiation of adult HSCs. Our results reveal that HSCs are able to differentiate into restricted progenitors, especially common myeloid, megakaryocyte-erythroid and pre-megakaryocyte progenitors, without undergoing cell division and even before entering the S phase of the cell cycle...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29761851/endocytosed-factor-v-is-trafficked-to-cd42b-proplatelet-extensions-during-differentiation-of-human-umbilical-cord-blood-derived-megakaryocytes
#10
Jacqueline M Gertz, Kelley C McLean, Beth A Bouchard
Plasma- and platelet-derived factor Va are essential for thrombin generation catalyzed by the prothrombinase complex; however, several observations demonstrate that the platelet-derived cofactor, which is formed following megakaryocyte endocytosis and modification of the plasma procofactor, factor V, is more hemostatically relevant. Factor V endocytosis, as a function of megakaryocyte differentiation and proplatelet formation, was assessed by flow cytometry and microscopy in CD34+ hematopoietic progenitor cells isolated from human umbilical cord blood and cultured for 12 days in the presence of cytokines to induce ex vivo differentiation into megakaryocytes...
May 15, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29760702/emerging-concepts-in-immune-thrombocytopenia
#11
REVIEW
Maurice Swinkels, Maaike Rijkers, Jan Voorberg, Gestur Vidarsson, Frank W G Leebeek, A J Gerard Jansen
Immune thrombocytopenia (ITP) is an autoimmune disease defined by low platelet counts which presents with an increased bleeding risk. Several genetic risk factors (e.g., polymorphisms in immunity-related genes) predispose to ITP. Autoantibodies and cytotoxic CD8+ T cells (Tc) mediate the anti-platelet response leading to thrombocytopenia. Both effector arms enhance platelet clearance through phagocytosis by splenic macrophages or dendritic cells and by induction of apoptosis. Meanwhile, platelet production is inhibited by CD8+ Tc targeting megakaryocytes in the bone marrow...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29752735/rbpi-21-opebacan-promotes-rapid-trilineage-hematopoietic-recovery-in-a-murine-model-of-high-dose-total-body-irradiation
#12
Kenneth J Janec, Huaiping Yuan, James E Norton, Rowan H Kelner, Christian K Hirt, Rebecca A Betensky, Eva C Guinan
The complexity of providing adequate care after radiation exposure has drawn increasing attention. While most therapeutic development has focused on improving survival at lethal radiation doses, acute hematopoietic syndrome (AHS) occurs at substantially lower exposures. Thus, it is likely that a large proportion of such a radiation-exposed population will manifest AHS of variable degree and that the medical and socioeconomic costs of AHS will accrue. Here, we examined the potential of rBPI21 (opebacan), used without supportive care, to accelerate hematopoietic recovery after radiation where expected survival was substantial (42-75%) at 30 days)...
May 11, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29751281/efficient-production-of-erythroid-megakaryocytic-and-myeloid-cells-using-single-cell-derived-ipsc-colony-differentiation
#13
Marten Hansen, Eszter Varga, Cathelijn Aarts, Tatjana Wust, Taco Kuijpers, Marieke von Lindern, Emile van den Akker
Hematopoietic differentiation of human induced pluripotent stem cells (iPSCs) provide opportunities not only for fundamental research and disease modelling/drug testing but also for large-scale production of blood effector cells for future clinical application. Although there are multiple ways to differentiate human iPSCs towards hematopoietic lineages, there is a need to develop reproducible and robust protocols. Here we introduce an efficient way to produce three major blood cell types using a standardized differentiation protocol that starts with a single hematopoietic initiation step...
April 28, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29747746/justicia-adhatoda-induces-megakaryocyte-differentiation-through-mitochondrial-ros-generation
#14
Usha Gutti, Jaswant Kumar Komati, Aneesh Kotipalli, Raja Gopal Venakata Saladi, Ravi Kumar Gutti
BACKGROUND: Hepatoprotective activity along with improved survival percentage and hematological parameters prior to whole body irradiation were reported with Justicia adhatoda extracts. PURPOSE: To evaluate the thrombopoietic potential of Justicia adhatoda L. leaf extract in megakaryocyte differentiation METHODS: Ethanol extracts were prepared using soxhlet extraction method, and IC50 value was determined. The effect of ethanol extracts obtained from Justicia adhatoda on megakaryocyte maturation and development in megakaryocytic Dami cell lines was tested...
April 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29743724/jak-map-kinase-pathway-activation-and-tp53-mutations-in-acute-leukemia-with-megakaryocytic-and-erythroid-differentiation
#15
Wenbin Xiao, Raajit Rampal, Yanming Zhang, Robert Cimera, Achim A Jungbluth, Maria Arcila, Mikhail Roshal, David C Park
No abstract text is available yet for this article.
April 24, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29741776/skewed-megakaryopoiesis-in-human-induced-pluripotent-stem-cell-derived-haematopoietic-progenitor-cells-harbouring-calreticulin-mutations
#16
Hiraku Takei, Yoko Edahiro, Shuichi Mano, Nami Masubuchi, Yoshihisa Mizukami, Misa Imai, Soji Morishita, Kyohei Misawa, Tomonori Ochiai, Satoshi Tsuneda, Hiroshi Endo, Sou Nakamura, Koji Eto, Akimichi Ohsaka, Marito Araki, Norio Komatsu
Somatic mutations in the calreticulin (CALR) gene have been found in most patients with JAK2- and MPL-unmutated Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). It has recently been shown that mutant CALR constitutively activates the thrombopoietin receptor MPL and, thus, plays a causal role in the development of MPNs. However, the roles of mutant CALR in human haematopoietic cell differentiation remain predominantly elusive. To examine the impact of the 5-base insertion mutant CALR gene (Ins5) on haematopoietic cell differentiation, we generated induced pluripotent stem cells from an essential thrombocythaemia (ET) patient harbouring a CALR-Ins5 mutation and from a healthy individual (WT)...
May 9, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29741246/high-throughput-sequencing-for-diagnosing-platelet-disorders-lessons-learned-from-exploring-the-causes-of-bleeding-disorders
#17
REVIEW
J Heremans, K Freson
Inherited platelet disorders (IPDs) are a heterogeneous group of disorders caused by multiple genetic defects. Obtaining a molecular diagnosis for IPD patients using a phenotype- and laboratory-based approach is complex, expensive, time-consuming, and not always successful. High-throughput sequencing (HTS) methods offer a genotype-based approach to facilitate molecular diagnostics. Such approaches are expected to decrease time to diagnosis, increase the diagnostic rate, and they have provided novel insights into the genotype-phenotype correlation of IPDs...
May 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29739118/investigation-of-iron-metabolism-for-regulating-megakaryopoiesis-and-platelet-count-according-to-the-mechanisms-of-anemia
#18
Suekyeung Kim, Sun Young Cho
BACKGROUND: Iron deficiency anemia (IDA) is characterized by depletion of total body iron stores or a poor supply of plasma iron. By contrast, chronic inflammation makes iron unavailable for hematopoiesis through a cytokinemediated cascade and leads to a condition known as anemia of chronic disease (AOC). However, the laboratory data regarding the regulatory role of iron metabolism on platelet count has not been fully discussed yet. In this study, we investigated the relationship between iron status and platelet production according to different anemic mechanisms representing different iron metabolisms...
March 1, 2018: Clinical Laboratory
https://www.readbyqxmd.com/read/29730354/the-nonreceptor-tyrosine-kinase-c-abl-phosphorylates-runx1-and-regulates-runx1-mediated-megakaryocyte-maturation
#19
Hainan Liu, Yan Cui, Guang-Fei Wang, Qincai Dong, Yebao Yao, Ping Li, Cheng Cao, Xuan Liu
The transcription factor Runx1 is an essential regulator of definitive hematopoiesis, megakaryocyte (MK) maturation, and lymphocyte differentiation. Runx1 mutations that interfere with its transcriptional activity are often present in leukemia patients. Recent work demonstrated that the transcriptional activity of Runx1 is regulated by kinase-mediated phosphorylation. In this study, we showed that c-Abl, but not Arg tyrosine kinase, associated with Runx1 both in cultured cells and in vitro. c-Abl-mediated tyrosine phosphorylation in the Runx1 transcription inhibition domain negatively regulated the transcriptional activity of Runx1 and inhibited Runx1-mediated MK maturation...
May 4, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29713553/acquired-amegakaryocytic-thrombocytopenia-and-pure-red-cell-aplasia-in-thymoma
#20
Sumit Dahal, Eliza Sharma, Suyash Dahal, Binav Shrestha, Bikash Bhattarai
Association of thymoma with myasthenia gravis, pure red cell aplasia, and aplastic anemia is well documented. However, thymoma complicated by acquired amegakaryocytic thrombocytopenia (AAMT) is rarely reported. Here, we present a case of a 60-year-old male with past medical history of recurrent invasive thymoma who presented with cough and blood in sputum. He was found to have severe normocytic normochromic anemia and thrombocytopenia that did not improve with intravenous steroids or multiple transfusions of red cells and platelets...
2018: Case Reports in Hematology
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