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https://www.readbyqxmd.com/read/29119850/dopamine-induces-platelet-production-from-megakaryocytes-via-oxidative-stress-mediated-signaling-pathways
#1
Shilei Chen, Mengjia Hu, Mingqiang Shen, Yang Xu, Cheng Wang, Xinmiao Wang, Fengju Li, Dongfeng Zeng, Fang Chen, Gaomei Zhao, Mo Chen, Fengchao Wang, Tianmin Cheng, Yongping Su, Jinghong Zhao, Song Wang, Junping Wang
Dopamine (DA), a catecholamine neurotransmitter, is known to for its diverse roles on hematopoiesis, yet its function in thrombopoiesis remains poorly understood. This study shows that DA stimulation can directly induce platelet production from megakaryocytes (MKs) in the final stages of thrombopoiesis via a reactive oxygen species (ROS)-dependent pathway. The mechanism was suggested by the results that DA treatment could significantly elevate the ROS levels in MKs, and time-dependently activate oxidative stress-mediated signaling, including p38 mitogen-activated protein kinase, c-Jun NH2-terminal kinase, and caspase-3 signaling pathways, while the antioxidants N-acetylcysteine and L-glutathione could effectively inhibit the activation of these signaling pathways, as well as the ROS increase and platelet production triggered by DA...
November 9, 2017: Platelets
https://www.readbyqxmd.com/read/29117572/deletion-of-glut1-and-glut3-reveals-multiple-roles-for-glucose-metabolism-in-platelet-and-megakaryocyte-function
#2
Trevor P Fidler, Robert A Campbell, Trevor Funari, Nicholas Dunne, Enrique Balderas Angeles, Elizabeth A Middleton, Dipayan Chaudhuri, Andrew S Weyrich, E Dale Abel
No abstract text is available yet for this article.
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29111429/megakaryocyte-and-polyploidization
#3
REVIEW
Stefania Mazzi, Larissa Lordier, Najet Debili, Hana Raslova, William Vainchenker
In mammals, platelets are produced in the blood by cytoplasmic fragmentation of megakaryocytes (MKs). Platelet production is thus dependent on both the MK number and size. During differentiation, MKs switch from a division by mitosis to polyploidization by endomitosis to increase their size. The endomitotic process includes several successive rounds of DNA replication with an entry in mitosis with a failure in late cytokinesis and a defect in karyokinesis. This leads to a giant cell with a modal ploidy at 16N and one multilobulated nucleus...
October 27, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/29109331/mkl1-mediates-tnf-%C3%AE-induced-pro-inflammatory-transcription-by-bridging-the-crosstalk-between-brg1-and-wdr5
#4
Wenping Xu, Quanyi Zhao, Min Wu, Mingming Fang, Yong Xu
Tumor necrosis factor alpha (TNF-α) is a cytokine that can potently stimulate the synthesis of a range of pro-inflammatory mediators in macrophages. The underlying epigenetic mechanism, however, is underexplored. Here we report that the transcriptional modulator megakaryocytic leukemia 1 (MKL1) is associated with a histone H3K4 methyltransferase activity. Re-ChIP assay suggests that MKL1 interacts with and recruits WDR5, a component of the COMPASS complex responsible for H3K4 methylation, to the promoter regions of pro-inflammatory genes in macrophages treated with TNF-α...
November 1, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/29104956/deletion-of-the-arp2-3-complex-in-megakaryocytes-leads-to-microthrombocytopenia-in-mice
#5
David S Paul, Caterina Casari, Congying Wu, Raymond Piatt, Swetha Pasala, Robert A Campbell, Kathryn O Poe, Dorsaf Ghalloussi, Robert H Lee, Jeremy D Rotty, Brian C Cooley, Kellie R Machlus, Joseph E Italiano, Andrew S Weyrich, James E Bear, Wolfgang Bergmeier
Actin reorganization regulates key processes in platelet activation. Here we examined the role of the Arp2/3 complex, an essential component in actin filament branching, in platelet function. The Arpc2 gene, encoding the p34 subunit of the Arp2/3 complex, was deleted in the megakaryocyte lineage (Arpc2(fl/fl)PF4-Cre). Deletion of the Arp2/3 complex resulted in marked microthrombocytopenia in mice, caused by premature platelet release into the bone marrow compartment and impaired platelet survival in circulation...
August 8, 2017: Blood Advances
https://www.readbyqxmd.com/read/29101237/human-notch4-is-a-key-target-of-runx1-in-megakaryocytic-differentiation
#6
Yueying Li, Chen Jin, Hao Bai, Yongxing Gao, Shu Sun, Lei Chen, Lei Qin, Paul P Liu, Linzhao Cheng, Qian-Fei Wang
Megakaryocytes (MKs) in adult marrow produce platelets that play important roles in blood coagulation and hemostasis. Monoallelic mutations of the master transcription factor gene RUNX1 lead to familial platelet disorder (FPD) characterized by defective MK and platelet development. However, the molecular mechanisms of FPD remain unclear. Previously, we generated human induced pluripotent stem cells (iPSCs) from patients with FPD containing a RUNX1 nonsense mutation. Production of MKs from the FPD-iPSCs was reduced, and targeted correction of the RUNX1 mutation restored MK production...
November 3, 2017: Blood
https://www.readbyqxmd.com/read/29097774/altered-b-lymphopoiesis-in-mice-with-deregulated-thrombopoietin-signaling
#7
Amanda E Au, Marion Lebois, Starling A Sim, Ping Cannon, Jason Corbin, Pradnya Gangatirkar, Craig D Hyland, Diane Moujalled, Angelika Rutgersson, Fatme Yassinson, Benjamin T Kile, Kylie D Mason, Ashley P Ng, Warren S Alexander, Emma C Josefsson
Thrombopoietin (TPO) is the master cytokine regulator of megakaryopoiesis. In addition to regulation of megakaryocyte and platelet number, TPO is important for maintaining proper hematopoietic stem cell (HSC) function. It was previously shown that a number of lymphoid genes were upregulated in HSCs from Tpo (-/-) mice. We investigated if absent or enhanced TPO signaling would influence normal B-lymphopoiesis. Absent TPO signaling in Mpl (-/-) mice led to enrichment of a common lymphoid progenitor (CLP) signature in multipotential lineage-negative Sca-1(+)c-Kit(+) (LSK) cells and an increase in CLP formation...
November 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29097382/gene-expression-and-risk-of-leukemic-transformation-in-myelodysplasia
#8
Yusuke Shiozawa, Luca Malcovati, Anna Gallì, Andrea Pellagatti, Mohsen Karimi, Aiko Sato-Otsubo, Yusuke Sato, Hiromichi Suzuki, Tetsuichi Yoshizato, Kenichi Yoshida, Yuichi Shiraishi, Kenichi Chiba, Hideki Makishima, Jacqueline Boultwood, Eva Hellström-Lindberg, Satoru Miyano, Mario Cazzola, Seishi Ogawa
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders with a highly variable prognosis. To identify a gene expression-based classification of myelodysplasia with biological and clinical relevance, we performed a comprehensive transcriptomic analysis of myeloid neoplasms with dysplasia using transcriptome sequencing. Unsupervised clustering of gene expression data of bone marrow CD34+ cells from 100 patients identified two subgroups. The first subtype was characterized by increased expression of genes related to erythroid/megakaryocytic (EMK) lineages, whereas the second subtype showed up-regulation of genes related to immature progenitor (IMP) cells...
November 2, 2017: Blood
https://www.readbyqxmd.com/read/29096349/extramedullary-hematopoiesis-mimicking-mediastinal-tumor-in-a-patient-with-hereditary-spherocytosis-case-report
#9
Jae Bum Park, Song Am Lee, Yo Han Kim, Woo Surng Lee, Jae Joon Hwang
INTRODUCTION: Extramedullary hematopoiesis (EMH) is a rare disorder, defined as the appearance of hematopoietic elements outside the bone marrow or peripheral blood. The exact mechanism of this development is still unknown. We herein report a case of intrathoracic EMH, manifesting as a posterior mediastinal tumor in a patient with hereditary spherocytosis. PRESENTATION OF CASE: A 45-year-old man who presented with anemia, jaundice and abdominal pain was diagnosed with hereditary spherocytosis...
October 27, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/29090618/increased-platelet-reactivity-as-measured-by-plasma-glycoprotein-vi-in-gout
#10
Richard Conway, Claire-Louise Murphy, Anne Madigan, Patricia Kavanagh, Liz Geraghty, Niamh Redmond, Laura Helbert, John J Carey, Eimear Dunne, Dermot Kenny, Geraldine M McCarthy
Patients with gout have an increased risk of cardiovascular events. The glycoprotein VI (GPVI) receptor is found exclusively on platelets and megakaryocytes, is proteolytically cleaved upon platelet activation, and detectable in plasma as soluble GPVI (sGPVI). Therefore, elevated sGPVI is a marker of platelet activation and a risk marker for cardiovascular events. The aim of this study was to assess platelet activation, as measured by plasma sGPVI level in gout. Blood samples were taken from patients with gout or osteoarthritis, and from healthy volunteers...
November 1, 2017: Platelets
https://www.readbyqxmd.com/read/29090484/mutations-of-the-integrin-%C3%AE-iib-%C3%AE-3-intracytoplasmic-salt-bridge-cause-macrothrombocytopenia-and-enlarged-platelet-%C3%AE-granules
#11
Marie Favier, Jean-Claude Bordet, Remi Favier, Vasiliki Gkalea, Xavier Pillois, Philippe Rameau, Najet Debili, Marie-Christine Alessi, Paquita Nurden, Hana Raslova, Alan Nurden
Rare gain-of-function mutations within the ITGA2B or ITGB3 genes have been recognized to cause macrothrombocytopenia (MTP). Here we report three new families with autosomal dominant (AD) MTP, two harboring the same mutation of ITGA2B, αIIbR995W, and a third family with an ITGB3 mutation, β3D723H. In silico analysis shows how the two mutated amino acids directly modify the salt bridge linking the intra-cytoplasmic part of αIIb to β3 of the integrin αIIbβ3. For all affected patients, the bleeding syndrome and MTP was mild to moderate...
November 1, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29089774/adult-acute-megakaryoblastic-leukemia-rare-association-with-cytopenias-of-undetermined-significance-and-p210-and-p190-bcr-abl-transcripts
#12
Delia Dima, Liana Oprita, Ana-Maria Rosu, Adrian Trifa, Cristina Selicean, Vlad Moisoiu, Ioana Frinc, Mihnea Zdrenghea, Ciprian Tomuleasa
Acute megakaryocytic leukemia (M7-AML) is a rare form of acute myeloid leukemia (AML), which is associated with poor prognosis. The case presented in the current report is a statement for the difficult diagnosis and clinical management of M7-AML in the context of a previous hematologic disorder of undetermined significance and associated genetic abnormalities. Probably, following the complete hematologic remission and further with induction chemotherapy plus tyrosine kinase inhibitor therapy, the clinical management of this case will be followed by a allogeneic bone marrow transplantation, the only proven therapy to improve overall survival...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29082099/label-free-monitoring-of-megakaryocytic-development-and-proplatelet-formation-in-vitro
#13
Dimitra Pouli, Lorenzo Tozzi, Carlo A Alonzo, Zhiyi Liu, David L Kaplan, Alessandra Balduini, Irene Georgakoudi
Megakaryopoiesis and platelet production are complex biological processes that require tight regulation of successive lineage commitment steps and are ultimately responsible for maintaining and renewing the pool of circulating platelets in the blood. Despite major advancements in the understanding of megakaryocytic biology, the detailed mechanisms driving megakaryocytic differentiation have yet to be elucidated. Here we show that automated image analysis algorithms applied to two-photon excited fluorescence (TPEF) images can non-invasively monitor structural and metabolic megakaryocyte behavior changes occurring during differentiation and platelet formation in vitro...
October 1, 2017: Biomedical Optics Express
https://www.readbyqxmd.com/read/29076133/effects-of-vascular-endothelial-growth-factors-and-their-receptors-on-megakaryocytes-and-platelets-and-related-diseases
#14
REVIEW
Jin-Gang Yang, Li-Li Wang, Dong-Chu Ma
It is well known that vascular endothelial growth factors (VEGFs) and their receptors (vascular endothelial growth factor receptors, VEGFRs) are expressed in different tissues, and VEGF-VEGFR loops regulate a wide range of responses, including metabolic homeostasis, cell proliferation, migration and tubuleogenesis. As ligands, VEGFs act on three structurally related VEGFRs (VEGFR1, VEGFR2 and VEGFR3 [also termed FLT1, KDR and FLT4, respectively]) that deliver downstream signals. Haematopoietic stem cells (HSCs), megakaryocytic cell lines, cultured megakaryocytes (MKs), primary MKs and abnormal MKs express and secrete VEGFs...
October 26, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29075489/intravascular-large-b-cell-lymphoma-associated-with-myelofibrosis-a-case-report
#15
Jong Gwon Choi, Hwan Hwi Cho, Sang Rok Kang, Se Min Jang, Eun Hyung Yoo, Hyun Jung Cho, Sun Moon Kim, Do Yeun Cho
Myelofibrosis (MF) is often accompanied by chronic myeloid leukemia, hairy cell leukemia, or certain primary myeloproliferative neoplasms, but is rarely associated with lymphoid neoplasms. We herein describe a case of intravascular large B-cell lymphoma (IVLBCL) with MF. IVLBCL is a rare, aggressive type of extranodal B-cell lymphoma, defined by proliferation of lymphomatous cells within small-to medium-sized vessels. A 60-year-old woman was admitted to the hospital with anemia, thrombocytopenia and fever. Bone marrow biopsy findings included trilineage hematopoiesis, increased numbers of immature cells, markedly abnormal and enlarged megakaryocytes, and diffuse fibrosis in multiple focal areas throughout the entire bone marrow space...
November 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29070140/-znf300-promotes-megakaryocytic-differentiation
#16
Jin Yu, Feng-Juan Yan, Cui-Juan Han, Jing-Yi Fan
OBJECTIVE: To study the function of ZNF300 in the megakaryocytes differentiation and proliferation. METHODS: Public data analysis of ZNF300 expression and megakaryocyte culture were used to reveal the correlation of ZNF300 expression with leukemia and megakaryocyte differetniation; ZNF300 overexpression was mediated by lentiviral or retroviral infection, and the differentiation and proliferation of K562 cells and primary mouse bone marrow cells to magekaryocytes were measured by flow cytometry, MTT assay and colony-forming test; the ZNF300 subcellular localization was tested by separating cytosolic and nuclear extracts combined with Western blotting...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29069738/hematopoietic-transcription-factors-and-differential-cofactor-binding-regulate-prkacb-isoform-expression
#17
Olga N Kuvardina, Stefanie Herkt, Annekarin Meyer, Lucas Schneider, Jasmin Yillah, Nicole Kohrs, Halvard Bonig, Erhard Seifried, Carsten Müller-Tidow, Jörn Lausen
Hematopoietic differentiation is controlled by key transcription factors, which regulate stem cell functions and differentiation. TAL1 is a central transcription factor for hematopoietic stem cell development in the embryo and for gene regulation during erythroid/megakaryocytic differentiation. Knowledge of the target genes controlled by a given transcription factor is important to understand its contribution to normal development and disease. To uncover direct target genes of TAL1 we used high affinity streptavidin/biotin-based chromatin precipitation (Strep-CP) followed by Strep-CP on ChIP analysis using ChIP promoter arrays...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29069007/successful-eltrombopag-treatment-of-severe-refractory-thrombocytopenia-in-chronic-myelomonocytic-leukemia-two-cases-reports-a-care-compliant-article
#18
Yayue Gao, Ming Gong, Chunxia Zhang, Xudong Kong, Yigai Ma
RATIONALE: Thrombocytopenia in chronic myelomonocytic leukemia (CMML) is usually attributed to impaired marrow production resulting from cytotoxic drug use or CMML itself ("CMML-induced thrombocytopenia"). In very rare cases, immune thrombocytopenia (ITP) can be a complication of CMML ("CMML-associated ITP"). However, treatment of severe thrombocytopenia in patients with CMML is still a challenge. PATIENT CONCERNS: Case 1 was a 61-year-old female patient admitted to our hospital because of skin petechiae and purpura for 6 days...
October 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29063121/-the-platelet-producing-function-of-lung
#19
Yan Zhou, Yan-Hong Huang, Zi-Qiang Luo
It is generally believed that platelets are cytoplasmic bodies with biological activity falling off the cytoplasm of megakaryocytes from bone marrow. However, a large number of megakaryocytes have been found in the lung tissue in many researches. Whether the lung has the function of producing platelets has been controversial. In this paper, we briefly review the proposition, early stage researches, the latest confirmations and possible meaning of the hypothesis of platelet-producing function of lung.
October 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/29057252/glis1-3-emerging-roles-in-reprogramming-stem-and-progenitor-cell-differentiation-and-maintenance
#20
REVIEW
David W Scoville, Hong Soon Kang, Anton M Jetten
Recent studies have provided evidence for a regulatory role of GLI-similar (GLIS) transcription factors in reprogramming, maintenance and differentiation of several stem and progenitor cell populations. GLIS1, in conjunction with several other reprogramming factors, was shown to markedly increase the efficiency of generating induced pluripotent stem cells (iPSC) from somatic cells. GLIS2 has been reported to contribute to the maintenance of the pluripotent state in hPSCs. In addition, GLIS2 has a function in regulating self-renewal of hematopoietic progenitors and megakaryocytic differentiation...
2017: Stem Cell Investigation
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