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Megakaryocyte

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https://www.readbyqxmd.com/read/28092904/cml-with-complex-chromosome-rearrangements-and-dysplastic-megakaryocytes
#1
Zhaodong Xu, Jean McGowan-Jordan
No abstract text is available yet for this article.
July 28, 2016: Blood
https://www.readbyqxmd.com/read/28092900/mimics-of-megakaryocytes-giant-bizarre-myeloma-cells
#2
Huifei Liu, Shaoying Li
No abstract text is available yet for this article.
August 11, 2016: Blood
https://www.readbyqxmd.com/read/28068330/loss-of-p53-induces-leukemic-transformation-in-a-murine-model-of-jak2-v617f-driven-polycythemia-vera
#3
T Tsuruta-Kishino, J Koya, K Kataoka, K Narukawa, Y Sumitomo, H Kobayashi, T Sato, M Kurokawa
As leukemic transformation of myeloproliferative neoplasms (MPNs) worsens the clinical outcome, reducing the inherent risk of the critical event in MPN cases could be beneficial. Among genetic alterations concerning the transformation, the frequent one is TP53 mutation. Here we show that retroviral overexpression of Jak2 V617F mutant into wild-type p53 murine bone marrow cells induced polycythemia vera (PV) in the recipient mice, whereas Jak2 V617F-transduced p53-null mice developed lethal leukemia after the preceding PV phase...
January 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28067429/lnk-deficiency-leads-to-tpo-mediated-osteoclastogenesis-and-increased-bone-mass-phenotype
#4
David J Olivos, Marta Alvarez, Ying-Hua Cheng, R Adam Hooker, Wendy A Ciovacco, Monique Bethel, Haley McGough, Christopher Yim, Brahmananda R Chitteti, Pierre P Eleniste, Mark C Horowitz, Edward F Srour, Angela Bruzzaniti, Robyn K Fuchs, Melissa A Kacena
The Lnk adapter protein negatively regulates the signaling of thrombopoietin (TPO), the main megakaryocyte (MK) growth factor. Lnk-deficient (-/-) mice have increased TPO signaling and increased MK number. Interestingly, several mouse models exist in which increased MK number leads to a high bone mass phenotype. Here we report the bone phenotype of these mice. MicroCT and static histomorphometric analyses at 20 weeks showed the distal femur of Lnk(-/-) mice to have significantly higher bone volume fraction and trabecular number compared to wild-type (WT) mice...
January 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28067095/progress-in-bio-manufacture-of-platelets-for-transfusion
#5
Shen Y Heazlewood, Susan K Nilsson, Kellie Cartledge, Cheang Ly Be, Andrew Vinson, Murat Gel, David N Haylock
Blood transfusion services face an ever-increasing demand for donor platelets to meet clinical needs. Whilst strategies for increasing platelet storage life and improving the efficiency of donor platelet collection are important, in the longer term, platelets generated by bio-manufacturing processes will be required to meet demands. Production of sufficient numbers of in vitro-derived platelets for transfusion represents a significant bioengineering challenge. In this review, we highlight recent progress in this area of research and outline the main technical and biological obstacles that need to be met before this becomes feasible and economic...
January 9, 2017: Platelets
https://www.readbyqxmd.com/read/28060252/transduction-transplantation-mouse-model-of-myeloproliferative-neoplasm
#6
Thanh Kim Nguyen, Sarah J Morse, Angela G Fleischman
Transduction-transplantation is a quick and efficient way to model human hematologic malignancies in mice. This technique results in expression of the gene of interest in hematopoietic cells and can be used to study the gene's role in normal and/or malignant hematopoiesis. This protocol provides a detailed description on how to perform transduction-transplantation using calreticulin (CALR) mutations recently identified in myeloproliferative neoplasm (MPN) as an example. In this protocol whole bone marrow cells from 5-flurouracil (5-FU) treated donor mice are transduced with a retrovirus encoding mutant CALR and transplanted into lethally irradiated syngeneic hosts...
December 22, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28059092/bone-marrow-morphology-and-disease-progression-in-congenital-thrombocytopenia-a-detailed-clinicopathologic-and-genetic-study-of-eight-cases
#7
Hamilton C Tsang, James B Bussel, Susan Mathew, Yen-Chun Liu, Allison A Imahiyerobo, Attilio Orazi, Julia T Geyer
Patients with congenital thrombocytopenia have an increased risk of developing myeloid neoplasms. In these cases, the morphologic distinction between disease at baseline and at progression is challenging. This report analyzes clinicopathologic features of congenital thrombocytopenia with long-term follow-up at one referral center. Records from the last 20 years were searched for cases of congenital thrombocytopenia with bone marrow biopsies and peripheral blood smears. The clinical, morphologic, immunophenotypic, and molecular features were analyzed...
January 6, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28057742/dual-role-of-il-21-in-megakaryopoiesis-and-platelet-homeostasis
#8
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/28053696/invasive-thymoma-with-pure-red-cell-aplasia-and-amegakaryocytic-thrombocytopenia
#9
Takuya Onuki, Yusuke Kiyoki, Sho Ueda, Masatoshi Yamaoka, Seiich Shimizu, Masaharu Inagaki
We here describe a case involving a 67-yearold female patient who was referred to our hospital due to severe anemia (hemoglobin, 5.0 g/dL), thrombocytopenia (platelet count, 0.6 × 10(4)/μL), and a mediastinal shadow with calcification noted on X-ray. On admission, an anterior mediastinal tumor was detected, and bone marrow biopsy revealed few megakaryocytes and severely reduced numbers of erythroid cells. The diagnosis was thymoma with pure red cell aplasia (PRCA) and acquired amegakaryocytic thrombocytopenia (AAMT)...
November 2, 2016: Hematology Reports
https://www.readbyqxmd.com/read/28052010/a-screen-for-fli-1-transcriptional-modulators-identifies-pkc-agonists-that-induce-erythroid-to-megakaryocytic-differentiation-and-suppress-leukemogenesis
#10
Tangjingjun Liu, Yao Yao, Gang Zhang, Ye Wang, Bin Deng, Jialei Song, Xiaogang Li, Fei Han, Xiao Xiao, Jue Yang, Lei Xia, You-Jun Li, Maksym Plachynta, Mu Zhang, Chen Yan, Shuzhen Mu, Heng Luo, Eldad Zacksenhaus, Xiaojiang Hao, Yaacov Ben-David
The ETS-related transcription factor Fli-1 affects many developmental programs including erythroid and megakaryocytic differentiation, and is frequently de-regulated in cancer. Fli-1 was initially isolated following retrovirus insertional mutagenesis screens for leukemic initiator genes, and accordingly, inhibition of this transcription factor can suppress leukemia through induction of erythroid differentiation. To search for modulators of Fli-1, we hereby performed repurposing drug screens with compounds isolated from Chinese medicinal plants...
December 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/28049729/the-plant-hormone-abscisic-acid-is-a-pro-survival-factor-in-human-and-murine-megakaryocytes
#11
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 proved to be secreted and active also in mammals, where it stimulates the activity of innate immune cells, of mesenchymal and hematopoietic stem cells and of insulin-releasing pancreatic β-cells through a signaling pathway involving the second messenger cyclic ADP-ribose (cADPR). In addition to behaving as an animal hormone, ABA holds promise also as nutraceutical plant-derived compound in humans...
January 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28043820/kinase-signaling-and-targeted-therapy-for-primary-myelofibrosis
#12
REVIEW
Qiong Yang, John D Crispino, Qiang Jeremy Wen
The myeloproliferative neoplasms (MPNs) are somatic mutation-driven hematological malignancies characterized by bone marrow fibrosis and the accumulation of atypical megakaryocytes with reduced polyploidization in the primary myelofibrosis (PMF) subtype of the MPNs. Increasing evidence points to a dominant role of abnormal megakaryocytes (MK) in disease initiation and progression. Here we review the literature related to kinase signaling pathways relevant to megakaryocyte differentiation and proliferation, including Aurora A kinase, RhoA/ROCK and JAK/STAT, as well as the activities of their targeted inhibitors in models of the disease...
December 30, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/28043314/hepatitis-b-leading-to-megaloblastic-anemia-and-catastrophic-peripheral-thrombocytopenia
#13
Muhammad Hafeez, Tariq Sarfraz, Raja Ghayas Khan, Abdul Rafe, Ghulam Rasool, Kamran Nazir Ahmed
Hepatitis B virus (HBV) typically causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma. It is associated with a variety of extrahepatic complications. We herein, present a rare extrahepatic complication of HBV infection. A 32-year man presented with melena, bleeding from gums and fever. Peripheral blood examination revealed anemia, macrocytosis and severe thrombocytopenia. His hepatitis B surface antigen (HBsAg) was positive but deoxyribonucleic acid (HBV DNA) by polymerase chain reaction (PCR) was negative...
December 2016: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/28038942/novel-thrombopoietin-mimetic-peptides-bind-c-mpl-receptor-synthesis-biological-evaluation-and-molecular-modeling
#14
Yaquan Liu, Fang Tian, Dejuan Zhi, Haiqing Wang, Chunyan Zhao, Hongyu Li
Thrombopoietin (TPO) acts in promoting the proliferation of hematopoietic stem cells and by initiating specific maturation events in megakaryocytes. Now, TPO-mimetic peptides with amino acid sequences unrelated to TPO are of considerable pharmaceutical interest. In the present paper, four new TPO mimetic peptides that bind and activate c-Mpl receptor have been identified, synthesized and tested by Dual-Luciferase reporter gene assay for biological activities. The molecular modeling research was also approached to understand key molecular mechanisms and structural features responsible for peptide binding with c-Mpl receptor...
December 20, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28035064/functional-assessment-of-von-willebrand-factor-expression-by-cancer-cells-of-non-endothelial-origin
#15
Anahita Mojiri, Konstantin Stoletov, Maria Areli Lorenzana Carrillo, Lian Willetts, Saket Jain, Roseline Godbout, Paul Jurasz, Consolato M Sergi, David D Eisenstat, John D Lewis, Nadia Jahroudi
Von Willebrand factor (VWF) is a highly adhesive procoagulant molecule that mediates platelet adhesion to endothelial and subendothelial surfaces. Normally it is expressed exclusively in endothelial cells (ECs) and megakaryocytes. However, a few studies have reported VWF detection in cancer cells of non-endothelial origin, including osteosarcoma. A role for VWF in cancer metastasis has long been postulated but evidence supporting both pro- and anti-metastatic roles for VWF has been presented. We hypothesized that the role of VWF in cancer metastasis is influenced by its cellular origin and that cancer cell acquisition of VWF expression may contribute to enhanced metastatic potential...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28034873/an-incomplete-trafficking-defect-to-the-cell-surface-leads-to-paradoxical-thrombocytosis-for-human-and-murine-mpl-p106l
#16
Fabrizia Favale, Kahia Messaoudi, Leila N Varghese, Siham Boukour, Christian Pecquet, Vitalina Gryshkova, Jean Philippe Defour, Roxana-Irina Albu, Olivier Bluteau, Paola Ballerini, Guy Leverger, Isabelle Plo, Najet Debili, Hana Raslova, Remi Favier, Stefan N Constantinescu, William Vainchenker
The mechanisms behind the hereditary thrombocytosis induced by the thrombopoietin (THPO) receptor MPL P106L mutant remain unknown. A complete trafficking defect to the cell surface has been reported, suggesting either weak constitutive activity or nonconventional THPO-dependent mechanisms. Here, we report that the thrombocytosis phenotype induced by MPL P106L belongs to the paradoxical group, where low MPL levels on platelets and mature megakaryocytes (MKs) lead to high serum THPO levels, whereas weak but not absent MPL cell-surface localization in earlier MK progenitors allows response to THPO by signaling and amplification of the platelet lineage...
December 29, 2016: Blood
https://www.readbyqxmd.com/read/28034281/is-there-any-role-for-splenectomy-in-adulthood-onset-chronic-immune-thrombocytopenia-in-the-era-of-tpo-receptors-agonists-a-critical-overview
#17
Vibor Milunovic, Inga Mandac Rogulj, Slobodanka Kolonic Ostojic
Immune thrombocytopenia (ITP) in adulthood is characterized by chronic relapsing course. Despite the efficacious first line treatment (corticosteroid, intravenous immunoglobulin), majority of patients will enter the chronic phase warranting another treatment approach. Until recently, splenectomy performed in ITP chronic phase represented the standard of care with long-term remissions in more than 70% of patients, but however has never been tested in clinical trials. However, with the advances of our understanding of ITP pathophysiology and the shifting focus on megakaryocyte impairment, novel drugs were introduced in treatment paradigm, mainly trombopoietin receptor agonists (TPO-RAs); romiplostim and eltrombopag...
December 29, 2016: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/28032520/differential-expression-of-sdf-1-receptor-cxcr4-in-molecularly-defined-forms-of-inherited-thrombocytopenias
#18
Juan P Salim, Ana C Glembotsky, Paola R Lev, Cecilia P Marin Oyarzún, Nora P Goette, Felisa C Molinas, Rosana F Marta, Paula G Heller
The SDF-1-CXCR4 axis plays an essential role in the regulation of platelet production, by directing megakaryocyte (MK) migration toward the vascular niche, thus allowing terminal maturation and proplatelet formation, and also regulates platelet function in an autocrine manner. Inherited thrombocytopenias (IT) comprise a spectrum of diverse clinical conditions caused by mutations in genes involved in platelet production and function. We assessed CXCR4 expression and SDF-1 levels in a panel of well-characterized forms of IT...
December 29, 2016: Platelets
https://www.readbyqxmd.com/read/28031160/myelo-erythroid-commitment-after-burn-injury-is-under-beta-adrenergic-control-via-mafb-regulation
#19
Shirin Hasan, Nicholas B Johnson, Michael J Mosier, Ravi Shankar, Peggie Conrad, Andrea Szilagyi, Richard L Gamelli, Kuzhali Muthumalaiappan
Severely injured burn patients receive multiple blood transfusions for anemia of critical illness despite the adverse consequences. One limiting factor to consider alternate treatment strategies is the lack of a reliable test platform to study molecular mechanisms of impaired erythropoiesis. This study illustrates how conditions resulting in high catecholamine microenvironment such as burns can instigate myelo-erythroid reprioritization influenced by beta-adrenergic stimulation leading to anemia. In mouse model of scald burn injury we observed, along with a 3-fold increase in bone marrow LSKs (lin(neg) Sca1(+)cKit(+)), the myeloid shift is accompanied with a significant reduction in megakaryocyte erythrocyte progenitors (MEPs)...
December 28, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28030481/thrombocytopenia-a-destruction-of-platelets
#20
Edythe M Greenberg
Platelets, or megakaryocytes, are irregular, disk-shaped cell fragments circulating in the blood. They are a primary component in maintaining hemostasis. Low platelet counts, or thrombocytopenia, leave patients at an increased risk of hemorrhage. This article discusses various etiologies of disorders of low platelets and current therapies for management.
January 2017: Journal of Infusion Nursing: the Official Publication of the Infusion Nurses Society
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