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https://www.readbyqxmd.com/read/28490570/mouse-runx1c-regulates-pre-megakaryocytic-erythroid-output-and-maintains-survival-of-megakaryocyte-progenitors
#1
Julia E Draper, Patrycja Sroczynska, Hui Sun Leong, Muhammad Z H Fadlullah, Crispin Miller, Valerie Kouskoff, Georges Lacaud
RUNX1 is crucial for the regulation of megakaryocyte specification, maturation and thrombopoiesis. Runx1 possesses two promoters: the distal P1 and proximal P2 promoters. The major protein isoforms generated by P1 and P2 are RUNX1C and RUNX1B respectively, which differ solely in their N-terminal amino acid sequences. RUNX1C is the most abundantly expressed isoform in adult hematopoiesis, present in all RUNX1-expressing populations, including the cKit(+) hematopoietic stem and progenitor cells (HSPCs). RUNX1B expression is more restricted, being highly expressed in the megakaryocyte lineage but downregulated during erythropoiesis...
May 10, 2017: Blood
https://www.readbyqxmd.com/read/28473904/from-chronic-immune-thrombocytopenia-to-severe-aplastic-anemia-recent-insights-into-the-evolution-of-eltrombopag
#2
REVIEW
Harinder Gill, Raymond S M Wong, Yok-Lam Kwong
Thrombopoietin (TPO) is the most potent cytokine stimulating thrombopoiesis. Therapy with exogenous TPO is limited by the formation of antibodies cross-reacting with endogenous TPO. Mimetics of TPO are compounds with no antigenic similarity to TPO. Eltrombopag is an orally-active nonpeptide small molecule that binds to the transmembrane portion of the TPO receptor MPL. Initial trials of eltrombopag have centered on immune thrombocytopenia (ITP), which is due to both increased destruction and decreased production of platelets...
May 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28449596/changes-in-platelet-count-and-size-indices-in-adolescent-patients-with-anorexia-nervosa
#3
Joanna Oświęcimska, Żaneta Malczyk, Agnieszka Szymlak, Agata Mikołajczak, Katarzyna Ziora, Jacek Zamlynski, Edyta Machura, Piotr Zajac, Bogdan Koczy, Alicja Kasperska-Zajac
The significance of platelet size indices has not been widely analyzed in anorexia nervosa (AN). It seems important to get more knowledge on the easily available indices of platelet function obtained by routine complete blood count analysis in patients with AN. We analyzed platelet count (PLT), platelet distribution width (PDW), and mean platelet volume using an automated blood cell counter in 25 females with AN and healthy age- and gender-matched nonatopic controls. Mean PLT was significantly lower in patients with AN than in the control group...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28432223/fli1-level-during-megakaryopoiesis-affects-thrombopoiesis-and-platelet-biology
#4
Karen K Vo, Danuta J Jarocha, Randolph B Lyde, Vincent Hayes, Christopher S Thom, Spencer K Sullivan, Deborah L French, Mortimer Poncz
Friend Leukemia Virus Integration 1 (FLI1), a critical transcription factor (TF) during megakaryocyte differentiation, is amongst genes hemizygously deleted in Jacobsen syndrome, resulting in a macrothrombocytopenia termed Paris-Trousseau syndrome (PTSx). Recently, heterozygote human FLI1 mutations have been ascribed to cause thrombocytopenia. We studied induced-pluripotent stem cell (iPSC)-derived megakaryocytes (iMegs) to better understand these clinical disorders, beginning with iPSCs generated from a PTSx patient and iPSCs from a control line with a targeted heterozygous FLI1 knockout (FLI1(+/-))...
April 21, 2017: Blood
https://www.readbyqxmd.com/read/28408900/the-thrombopoietin-receptor-structural-basis-of-traffic-and-activation-by-ligand-mutations-agonists-and-mutated-calreticulin
#5
REVIEW
Leila N Varghese, Jean-Philippe Defour, Christian Pecquet, Stefan N Constantinescu
A well-functioning hematopoietic system requires a certain robustness and flexibility to maintain appropriate quantities of functional mature blood cells, such as red blood cells and platelets. This review focuses on the cytokine receptor that plays a significant role in thrombopoiesis: the receptor for thrombopoietin (TPO-R; also known as MPL). Here, we survey the work to date to understand how this receptor functions at a molecular level throughout its lifecycle, from traffic to the cell surface, dimerization and binding cognate cytokine via its extracellular domain, through to its subsequent activation of associated Janus kinases and initiation of downstream signaling pathways, as well as the regulation of these processes...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28391511/normal-and-pathological-dynamics-of-platelets-in-humans
#6
Gabriel P Langlois, Morgan Craig, Antony R Humphries, Michael C Mackey, Joseph M Mahaffy, Jacques Bélair, Thibault Moulin, Sean R Sinclair, Liangliang Wang
We develop a mathematical model of platelet, megakaryocyte, and thrombopoietin dynamics in humans. We show that there is a single stationary solution that can undergo a Hopf bifurcation, and use this information to investigate both normal and pathological platelet production, specifically cyclic thrombocytopenia. Carefully estimating model parameters from laboratory and clinical data, we then argue that a subset of parameters are involved in the genesis of cyclic thrombocytopenia based on clinical information...
April 8, 2017: Journal of Mathematical Biology
https://www.readbyqxmd.com/read/28388313/arachidonic-acid-and-docosahexanoic-acid-enhance-platelet-formation-from-human-apheresis-derived-cd34-cells
#7
Ankita Dhenge, Kedar Limbkar, Sameer Melinkeri, Vaijayanti Prakash Kale, Lalita Limaye
An Aberration in megakaryopoiesis and thrombopoiesis, 2 important processes that maintain hemostasis, leads to thrombocytopenia. Though platelet transfusions are used to treat this condition, blood banks frequently face a shortage of platelets. Therefore, methods to generate platelets on a large scale are strongly desirable. However, to generate megakaryocytes (MKs) and platelets (PLTs) in numbers sufficient for clinical application, it is essential to understand the mechanism of platelet production and explore efficient strategies accordingly...
April 7, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28279968/newly-formed-reticulated-platelets-undermine-pharmacokinetically-short-lived-antiplatelet-therapies
#8
Paul C Armstrong, Thomas Hoefer, Rebecca B Knowles, Arthur T Tucker, Melissa A Hayman, Plinio M Ferreira, Melissa V Chan, Timothy D Warner
OBJECTIVE: Aspirin together with thienopyridine P2Y12 inhibitors, commonly clopidogrel, is a cornerstone of antiplatelet therapy. However, many patients receiving this therapy display high on-treatment platelet reactivity, which is a major therapeutic hurdle to the prevention of recurrent thrombotic events. The emergence of uninhibited platelets after thrombopoiesis has been proposed as a contributing factor to high on-treatment platelet reactivity. Here, we investigate the influences of platelet turnover on platelet aggregation in the face of different dual-antiplatelet therapy strategies...
May 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28253829/emerging-drugs-for-immune-thrombocytopenia-itp
#9
Abdulgabar Salama
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by autoantibody production against platelets, increased platelet destruction, and, in some cases, impaired thrombopoiesis. The majority of affected patients have significant bleeding risks due to low platelet counts and require treatment. The etiology of ITP is an immunological labyrinth. Currently available treatment options are usually not only nonspecific, but are also associated with some risks. Areas covered: Several useful drugs for the treatment of ITP are currently available...
March 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/28149021/prevalence-of-factor-v-leiden-g1691a-and-mthfr-c677t-thrombosis-gene-modifier-in-iron-deficiency-anemia-a-pathophysiological-effect-in-indian-isolates
#10
S K Pandey, S Pandey, R M Mishra, M Indurkar
Normal iron levels are required to prevent thrombocytosis by inhibiting thrombopoiesis. Thrombocytosis is usually associated with a mild iron deficiency and is the result of a lack of inhibition of thrombopoiesis. Study participants were 430 iron deficiency anemia (IDA) patients. Ten (10) mL of venous blood were collected for the subjects. Ferritin analysis was done by ELISA method while Hemogram analysis was done by auto-analyzer. Factor V Leiden, PRTG20210A, and MTHFR C677T genotype analysis was performed by PCR-RFLP method...
March 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28112988/platelet-bioreactor-accelerated-evolution-of-design-and-manufacture
#11
Jonathan N Thon, Brad J Dykstra, Lea M Beaulieu
Platelets, responsible for clot formation and blood vessel repair, are produced by megakaryocytes in the bone marrow. Platelets are critical for hemostasis and wound healing, and are often provided following surgery, chemotherapy, and major trauma. Despite their importance, platelets today are derived exclusively from human volunteer donors. They have a shelf life of just five days, making platelet shortages common during long weekends, civic holidays, bad weather, and during major emergencies when platelets are needed most...
January 23, 2017: Platelets
https://www.readbyqxmd.com/read/28057742/dual-role-of-il-21-in-megakaryopoiesis-and-platelet-homeostasis
#12
Salima Benbarche, Catherine Strassel, Catherine Angénieux, Léa Mallo, Monique Freund, Christian Gachet, François Lanza, Henri de la Salle
Gene profiling studies have indicated that in vitro differentiated human megakaryocytes express the receptor for IL-21 (IL-21R), an immunostimulatory cytokine associated with inflammatory disorders and currently under evaluation in cancer therapy. The aim of this study was to investigate whether IL-21 modulates megakaryopoiesis. We first checked the expression of IL-21 receptor on human bone marrow and in vitro differentiated megakaryocytes. Then, we investigated the effect of IL-21 on the in vitro differentiation of human blood CD34+ progenitors into megakaryocytes...
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28049729/the-plant-hormone-abscisic-acid-is-a-prosurvival-factor-in-human-and-murine-megakaryocytes
#13
Alessandro Malara, Chiara Fresia, Christian Andrea Di Buduo, Paolo Maria Soprano, Francesco Moccia, Cesare Balduini, Elena Zocchi, Antonio De Flora, Alessandra Balduini
Abscisic acid (ABA) is a phytohormone involved in pivotal physiological functions in higher plants. Recently, ABA has been proven to be also secreted and active in mammals, where it stimulates the activity of innate immune cells, mesenchymal and hematopoietic stem cells, and insulin-releasing pancreatic β cells through a signaling pathway involving the second messenger cyclic ADP-ribose (cADPR). In addition to behaving like an animal hormone, ABA also holds promise as a nutraceutical plant-derived compound in humans...
February 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28033261/elevated-thrombopoietin-and-platelet-indices-confirm-active-thrombopoiesis-but-fail-to-predict-clinical-severity-of-puumala-hantavirus-infection
#14
Outi Laine, Lotta Joutsi-Korhonen, Riitta Lassila, Heini Huhtala, Antti Vaheri, Satu Mäkelä, Jukka Mustonen
We evaluated the mechanisms of thrombocytopenia and procoagulant changes in relation with clinical variables in a cohort of patients with acute hantavirus disease.Blood samples of 33 prospectively recruited, consecutive, hospitalized patients with acute Puumala virus-induced hemorrhagic fever with renal syndrome (HFRS) were collected acutely and at the recovery visit (control). Serum thrombopoietin (TPO) and activity of plasma microparticles (MPs) from various cell sources were measured with enzyme-linked immunosorbent assay-based methods...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27941645/pathophysiological-significance-of-store-operated-calcium-entry-in-megakaryocyte-function-opening-new-paths-for-understanding-the-role-of-calcium-in-thrombopoiesis
#15
REVIEW
Christian A Di Buduo, Alessandra Balduini, Francesco Moccia
Store-Operated Calcium Entry (SOCE) is a universal calcium (Ca(2+)) influx mechanism expressed by several different cell types. It is now known that Stromal Interaction Molecule (STIM), the Ca(2+) sensor of the intracellular compartments, together with Orai and Transient Receptor Potential Canonical (TRPC), the subunits of Ca(2+) permeable channels on the plasma membrane, cooperate in regulating multiple cellular functions as diverse as proliferation, differentiation, migration, gene expression, and many others, depending on the cell type...
December 8, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27860293/thrombocytopenia-in-chronic-liver-disease
#16
REVIEW
Markus Peck-Radosavljevic
Thrombocytopenia is a common haematological disorder in patients with chronic liver disease. It is multifactorial and severity of liver disease is the most influential factor. As a result of the increased risk of bleeding, thrombocytopenia may impact upon medical procedures, such as surgery or liver biopsy. The pathophysiology of thrombocytopenia in chronic liver disease has long been associated with the hypothesis of hypersplenism, where portal hypertension causes pooling and sequestration of all corpuscular elements of the blood, predominantly thrombocytes, in the enlarged and congested spleen...
November 17, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/27786336/the-hippo-pathway-regulates-human-megakaryocytic-differentiation
#17
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/27775788/local-bone-marrow-renin-angiotensin-system-in-the-genesis-of-leukemia-and-other-malignancies
#18
I C Haznedaroglu, U Y Malkan
The existence of a local renin-angiotensin system (RAS) specific to the hematopoietic bone marrow (BM) microenvironment had been proposed two decades ago. Most of the RAS molecules including ACE, ACE2, AGT, AGTR1, AGTR2, AKR1C4, AKR1D1, ANPEP, ATP6AP2, CMA1, CPA3, CTSA, CTSD, CTSG, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, DPP3, EGFR, ENPEP, GPER, HSD11B1, HSD11B2, IGF2R, KLK1, LNPEP, MAS1, MME, NR3C1, NR3C2, PREP, REN, RNPEP, and THOP1 are locally present in the BM microenvironment. Local BM RAS peptides control the hematopoietic niche, myelopoiesis, erythropoiesis, thrombopoiesis and the development of other cellular lineages...
October 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27766065/thrombopoietin-and-its-receptor-in-normal-and-neoplastic-hematopoiesis
#19
Kenneth Kaushansky
Thrombopoietin was posited to exist in 1958 and cloned in 1994, and in the ensuing two decades we have learned a great deal about the physiology and pathology of the primary regulator of thrombopoiesis. This paper will review the role of the hormone and its receptor, the product of the c-Mpl proto-oncogene, in health and disease, including many unexpected effects in both normal and neoplastic hematopoiesis. Amongst these unexpected properties are a non-redundant effect on hematopoietic stem cells, a critical role in all three of the acquired, chronic myeloproliferative neoplasms, as well as both gain-of-function and loss-of-function mutations in congenital and acquired states of thrombocytopenia and thrombocythemia...
2016: Thrombosis Journal
https://www.readbyqxmd.com/read/27748371/estrogen-promotes-megakaryocyte-polyploidization-via-estrogen-receptor-beta-mediated-transcription-of-gata1
#20
C Du, Y Xu, K Yang, S Chen, X Wang, S Wang, C Wang, M Shen, F Chen, M Chen, D Zeng, F Li, T Wang, F Wang, J Zhao, G Ai, T Cheng, Y Su, J Wang
Estrogen is reported to be involved in thrombopoiesis and the disruption of its signaling may cause myeloproliferative disease, yet the underlying mechanisms remain largely unknown. GATA-binding factor 1 (GATA1) is a key regulator of megakaryocyte (MK) differentiation and its deficiency will lead to megakaryoblastic leukemia. Here we show that estrogen can dose-dependently promote MK polyploidization and maturation via activation of estrogen receptor beta (ERβ), accompanied by a significant upregulation of GATA1...
April 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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