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https://www.readbyqxmd.com/read/28213379/slowed-decay-of-mrnas-enhances-platelet-specific-translation
#1
Eric W Mills, Rachel Green, Nicholas T Ingolia
Platelets are anucleate cytoplasmic fragments that lack genomic DNA, but continue to synthesize protein using a pool of mRNAs, ribosomes, and regulatory small RNAs inherited from the precursor megakaryocyte (MK). The regulatory processes that shape the platelet transcriptome and the full scope of platelet translation have remained elusive. Using RNA-Seq and ribosome profiling of primary human platelets, we show the platelet transcriptome encompasses a subset of transcripts detected by RNA-Seq analysis of in vitro derived MK cells and these platelet-enriched transcripts are broadly occupied by ribosomes...
February 17, 2017: Blood
https://www.readbyqxmd.com/read/28211870/non-apoptotic-functions-of-caspases-in-myeloid-cell-differentiation
#2
REVIEW
Stéphanie Solier, Michaela Fontenay, William Vainchenker, Nathalie Droin, Eric Solary
Subtle caspase activation is associated with the differentiation of several myeloid lineages. A tightly orchestrated dance between caspase-3 activation and the chaperone HSP70 that migrates to the nucleus to protect the master regulator GATA-1 from cleavage transiently occurs in basophilic erythroblasts and may prepare nucleus and organelle expel that occurs at the terminal phase of erythroid differentiation. A spatially restricted activation of caspase-3 occurs in maturing megakaryocytes to promote proplatelet maturation and platelet shedding in the bloodstream...
February 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28211564/the-genomics-of-inherited-bone-marrow-failure-from-mechanism-to-the-clinic
#3
REVIEW
Talia Wegman-Ostrosky, Sharon A Savage
The inherited bone marrow failure syndromes (IBMFS) typically present with significant cytopenias in at least one haematopoietic cell lineage that may progress to pancytopenia, and are associated with increased risk of cancer. Although the clinical features of the IBMFS are often diagnostic, variable disease penetrance and expressivity may result in diagnostic dilemmas. The discovery of the genetic aetiology of the IBMFS has been greatly facilitated by next-generation sequencing methods. This has advanced understanding of the underlying biology of the IBMFS and been essential in improving clinical management and genetic counselling for affected patients...
February 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28209755/sanada-c-xavier-ferrucio-j-lu-y-c-et-al-adult-human-megakaryocyte-erythroid-progenitors-are-in-the-cd34-cd38-mid-fraction-blood-2016-128-7-923-933
#4
(no author information available yet)
No abstract text is available yet for this article.
February 16, 2017: Blood
https://www.readbyqxmd.com/read/28208757/pathogenesis%C3%A2-and%C3%A2-therapeutic%C3%A2-mechanisms%C3%A2-in%C3%A2-immune%C3%A2-thrombocytopenia%C3%A2-itp
#5
REVIEW
Anne Zufferey, Rick Kapur, John W Semple
Immune thrombocytopenia (ITP) is a complex autoimmune disease characterized by low  platelet counts. The pathogenesis of ITP remains unclear although both antibody-mediated and/or  T cell-mediated platelet destruction are key processes. In addition, impairment of T cells, cytokine  imbalances, and the contribution of the bone marrow niche have now been recognized to be  important. Treatment strategies are aimed at the restoration of platelet counts compatible with  adequate hemostasis rather than achieving physiological platelet counts...
February 9, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28205462/atypical-chronic-myeloid-leukemia-in-a-german-shepherd-dog
#6
Christina L Marino, Jimmy N S N Tran, Tracy Stokol
A 4-y-old neutered male German Shepherd Dog was presented with a 3-d duration of lethargy, restlessness, and vomiting. Physical examination revealed generalized lymphadenopathy, pale mucous membranes, systolic heart murmur, dehydration, and fever. Hematologic abnormalities included moderate-to-marked leukocytosis, characterized by neutrophilia with a left shift to progranulocytes and 2% presumptive myeloid blasts, marked anemia that was nonregenerative, and marked thrombocytopenia. Dysplasia was evident in neutrophils and platelets...
February 1, 2017: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/28202531/the-role-of-megakaryocytes-in-breast-cancer-metastasis-to-bone
#7
Walter Jackson, Donna M Sosnoski, Sara E Ohanessian, Paige Chandler, Adam W Mobley, Kacey D Meisel, Andrea M Mastro
Little is known about how megakaryocytes affect metastasis apart from serving as the source of platelets. We noted an increase in the number of megakaryocytes in the femurs of metastases-bearing athymic mice four weeks following intracardiac inoculation of MDA-MB-231 human breast cancer cells. How did the megakaryocytes relate to the metastases? Did megakaryocytes prepare a niche or did they increase in response to metastases? To test these possibilities, we examined two models of experimental metastasis, intracardiac inoculation of human MDA-MB-231 into athymic mice, and intramammary injection of mouse tumor cells, 4T1...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28194057/clinical-characteristics-and-prognosis-of-167-cases-of-acute-erythroleukemia
#8
Zhi-Qiang Ma, Ji-Hong Pan, Da-Xin Jing, Chong-Yan Xu
To observe the biological characteristic and the prognoses in patients with acute erythroleukemia (AEL). The results of 167 patients with newly diagnosed AEL, from January 2004 and June 2014 in the department of Hematology, Shandong Province Chinese Medicine Hospital, were reviewed by morphology, immunology, cytogenetics, molecular biology. Flow cytometry analysis indicated that CD13 (96.1 %), CD33 (95.1 %), CD117 (87.4 %) and CD34 (79.4 %) were highly expressed in AEL. 56 of 148 (37.8 %) AEL patients had a variety of cytogenetic abnormalities, 27 of 148 (18...
March 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28188970/refractory-anemia-with-ring-sideroblasts-rars-and-rars-with-thrombocytosis-rars-t-2017-update-on-diagnosis-risk-stratification-and-management
#9
Mrinal M Patnaik, Ayalew Tefferi
DISEASE OVERVIEW: Ring sideroblasts (RS) are erythroid precursors with abnormal perinuclear mitochondrial iron accumulation. Two myeloid neoplasms defined by the presence of RS, include refractory anemia with ring sideroblasts (RARS), now classified under myelodysplastic syndromes with RS (MDS-RS) and RARS with thrombocytosis (RARS-T); now called myelodysplastic/myeloproliferative neoplasm with RS and thrombocytosis (MDS/MPN-RS-T). DIAGNOSIS: MDS-RS is a lower risk MDS, with single or multilineage dysplasia (SLD/MLD), <5% bone marrow (BM) blasts and ≥15% BM RS (≥5% in the presence of SF3B1 mutations)...
March 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28179275/granulocyte-colony-stimulating-factor-mobilizes-dormant-hematopoietic-stem-cells-without-proliferation-in-mice
#10
Jeffrey M Bernitz, Michael Daniel, Yesai S Fstkchyan, Kateri Moore
Granulocyte colony stimulating factor (G-CSF) is used clinically to treat leukopenia and to enforce hematopoietic stem cell (HSC) mobilization to the peripheral blood (PB). However, G-CSF is also produced in response to infection, and excessive exposure reduces HSC repopulation capacity. Previous work has shown that dormant HSCs contain all the long-term repopulation potential in the bone marrow (BM), and that as HSCs accumulate a divisional history they progressively lose regenerative potential. As G-CSF treatment also induces HSC proliferation, we sought to examine whether G-CSF-mediated repopulation defects are due to increased proliferative history...
February 8, 2017: Blood
https://www.readbyqxmd.com/read/28174417/amkl-chimeric-transcription-factors-are-potent-inducers-of-leukemia
#11
J Dang, S Nance, J Ma, J Cheng, M P Walsh, P Vogel, J Easton, G Song, M Rusch, A L Gedman, C Koss, J R Downing, T A Gruber
Acute megakaryoblastic leukemia in patients without Down syndrome is a rare malignancy with a poor prognosis. RNA sequencing of fourteen pediatric cases previously identified novel fusion transcripts that are predicted to be pathologic including CBFA2T3-GLIS2, GATA2-HOXA9, MN1-FLI, and NIPBL-HOXB9. In contrast to CBFA2T3-GLIS2 which is insufficient to induce leukemia, we demonstrate that the introduction of GATA2-HOXA9, MN1-FLI1 or NIPBL-HOXB9 into murine bone marrow induces overt disease in syngeneic transplant models...
February 8, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28164843/megakaryocytic-microparticles-for-targeted-delivery-to-hematopoietic-stem-cells
#12
EDITORIAL
Kinam Park
No abstract text is available yet for this article.
February 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28159675/transforming-growth-factor-%C3%AE-and-interleukin-13-producing-mast-cells-are-associated-with-fibrosis-in-bone-marrow
#13
Shoko Nakayama, Taiji Yokote, Nobuya Hiraoka, Toshikazu Akioka, Uta Nishiwaki, Takuji Miyoshi, Kazuki Iwaki, Ayami Fumimoto, Yuki Masuda, Jun Hatooka, Mayumi Fujimoto, Yasuichiro Nishimura, Motomu Tsuji
Although bone marrow fibrosis is a lethal condition, its underlying mechanism is not fully understood. This study aimed to investigate the pathogenesis of fibrosis in the bone marrow through histological examination of mast cell infiltration and the expression of fibrosis-associated cytokines. We analyzed 22 bone marrows with fibrosis [eight primary myelofibrosis (PMF), five post-essential thrombocythemia (ET) myelofibrosis (MF), and nine myelodysplastic syndrome (MDS) with bone marrow fibrosis (BMF)]. Immunohistochemical and immunofluorescence staining were performed using anti-mast cell tryptase, interleukin (IL)-13, transforming growth factor-beta (TGF-β), CD34, and CD42b antibodies...
January 31, 2017: Human Pathology
https://www.readbyqxmd.com/read/28157629/the-epigenetically-regulated-mir-34a-targeting-c-src-suppresses-raf-mek-erk-signaling-pathway-in-k-562-cells
#14
Yang Yang, Li Ding, Zi-Kuan Guo, Xiao-Li Zheng, Li-Sheng Wang, Hui-Yan Sun, Zhan-Guo Jin, Heng-Xiang Wang
Previous reports show that miR-34a suppressed K-562 cell proliferation and contributed to megakaryocytic differentiation of K-562 cells. Here, we reported that miR-34a, a tumor suppressor gene, is down-regulated in the K-562 cells and chronic myeloid leukemia (CML) patients due to aberrant DNA hypermethylation. c-SRC is a target of miR-34a. Restoring miR-34a expression resulted in down-regulation of c-SRC and phosphorylated (Tyr416) c-SRC protein in K-562 cells, which consequently triggered suppression of the RAF/MEK/ERK signaling pathway to decrease cell proliferation...
January 22, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28145579/spontaneous-mediastinal-myeloid-sarcoma-in-a-common-marmoset-callithrix-jacchus-and-review-of-the-veterinary-literature
#15
REVIEW
Danielle T Morosco, Curtis R Cline, Michael A Owston, Shyamesh Kumar, Edward J Dick
BACKGROUND: Myeloid sarcoma is a rare manifestation of myeloproliferative disorder defined as an extramedullary mass composed of myeloid precursor cells. A 9-month old, female, common marmoset (Callithrix jacchus) had increased respiratory effort. METHODS: A complete necropsy with histology and immunohistochemistry was performed. RESULTS: The thymus was replaced by a firm, gray-tan mass with a faint green tint, filling over 50% of the thoracic cavity...
February 1, 2017: Journal of Medical Primatology
https://www.readbyqxmd.com/read/28144286/study-of-clinical-haematological-and-cytogenetic-profile-of-patients-with-acute-erythroid-leukaemia
#16
Jacob Abraham Linu, Ms Namratha Udupa, D S Madhumathi, K C Lakshmaiah, K Govind Babu, D Lokanatha, Mc Suresh Babu, K N Lokesh, L K Rajeev, A H Rudresha
BACKGROUND: Acute erythroid leukaemia (AEL) is a rare subtype of acute myeloid leukaemia (AML), constituting <5% of all the cases of AML. The World Health Organization (WHO) in 2001 classified AEL into two types: (1) erythroid/myeloid leukaemia which required ≥50% erythroid precursors with ≥20% of the non-erythroid cells to be myeloid blasts and (2) pure erythroleukemia (pEL) with ≥80% erythroblasts. The WHO 2008 classification kept these subcategories, but made erythroleukemia a diagnosis of exclusion...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28139814/von-willebrand-factor-processing
#17
Maria A Brehm
Von Willebrand factor (VWF) is a multimeric glycoprotein essential for primary haemostasis that is produced only in endothelial cells and megakaryocytes. Key to VWF's function in recruitment of platelets to the site of vascular injury is its multimeric structure. The individual steps of VWF multimer biosynthesis rely on distinct posttranslational modifications at specific pH conditions, which are realized by spatial separation of the involved processes to different cell organelles. Production of multimers starts with translocation and modification of the VWF prepropolypeptide in the endoplasmic reticulum to produce dimers primed for glycosylation...
January 31, 2017: Hämostaseologie
https://www.readbyqxmd.com/read/28138994/megakaryocyte-expansion-and-macrophage-infiltration-in-bone-marrow-of-rats-subchronically-treated-with-mnx-n-nitroso-environmental-degradation-product-of-munitions-compound-rdx-hexahydro-1-3-5-trinitro-1-3-5-triazine
#18
Sindhura Ramasahayam, Sridhar Jaligama, Sahar M Atwa, Joshua T Salley, Marissa Thongdy, Benny L Blaylock, Sharon A Meyer
Hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX), environmental degradation product of munitions hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), causes seizures in rats with acute oral exposure like parent RDX. Our previous studies have additionally reported hematotoxicity with acute MNX exposure manifested as myelosuppression, anemia and splenic hemosiderosis. This study explored whether MNX administered subchronically continued to target bone marrow to elicit peripheral blood cytopenia. Female Sprague-Dawley rats were gavaged daily for 4 or 6 weeks with 47 mg kg(-1)  day(-1) MNX (¼ LD50 ) or vehicle (5% dimethyl sulfoxide in corn oil) and hematological and clinical chemistry parameters, spleen weights, spleen and bone marrow histopathology and immunohistochemistry with ED1 anti-CD68 macrophage marker were evaluated 24 h after the last dose...
January 31, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28135282/mesenchymal-cell-reprogramming-in-experimental-mplw515l-mouse-model-of-myelofibrosis
#19
Ying Han, Lanzhu Yue, Max Wei, Xiubao Ren, Zonghong Shao, Ling Zhang, Ross L Levine, Pearlie K Epling-Burnette
Myelofibrosis is an indicator of poor prognosis in myeloproliferative neoplasms (MPNs), but the precise mechanism(s) contributing to extracellular matrix remodeling and collagen deposition in the bone marrow (BM) niche remains unanswered. In this study, we isolated mesenchymal stromal cells (MSCs) from mice transplanted with wild-type thrombopoietin receptor (MPLWT) and MPLW515L retroviral-transduced bone marrow. Using MSCs derived from MPLW515-transplant recipients, excessive collagen deposition was maintained in the absence of the virus and neoplastic hematopoietic cells suggested that the MSCs were reprogrammed in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28134622/mutations-in-tropomyosin-4-underlie-a-rare-form-of-human-macrothrombocytopenia
#20
Irina Pleines, Joanne Woods, Stephane Chappaz, Verity Kew, Nicola Foad, José Ballester-Beltrán, Katja Aurbach, Chiara Lincetto, Rachael M Lane, Galina Schevzov, Warren S Alexander, Douglas J Hilton, William J Astle, Kate Downes, Paquita Nurden, Sarah K Westbury, Andrew D Mumford, Samya G Obaji, Peter W Collins, Fabien Delerue, Lars M Ittner, Nicole S Bryce, Mira Holliday, Christine A Lucas, Edna C Hardeman, Willem H Ouwehand, Peter W Gunning, Ernest Turro, Marloes R Tijssen, Benjamin T Kile
Platelets are anuclear cells that are essential for blood clotting. They are produced by large polyploid precursor cells called megakaryocytes. Previous genome-wide association studies in nearly 70,000 individuals indicated that single nucleotide variants (SNVs) in the gene encoding the actin cytoskeletal regulator tropomyosin 4 (TPM4) exert an effect on the count and volume of platelets. Platelet number and volume are independent risk factors for heart attack and stroke. Here, we have identified 2 unrelated families in the BRIDGE Bleeding and Platelet Disorders (BPD) collection who carry a TPM4 variant that causes truncation of the TPM4 protein and segregates with macrothrombocytopenia, a disorder characterized by low platelet count...
January 30, 2017: Journal of Clinical Investigation
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