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Experimental Hematology

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https://www.readbyqxmd.com/read/28238806/rat-acute-gvhd-is-th1-driven-and-characterized-by-predominant-donor-cd4-t-cell-infiltration-of-skin-and-gut
#1
Margherita Boieri, Pranali Shah, Dasaradha Jalapothu, Olena Zaitseva, Lutz Walter, Bent Rolstad, Christian Naper, Ralf Dressel, Marit Inngjerdingen
Acute graft-versus-host disease (aGvHD) remains a significant hurdle to successful treatment of many hematological disorders. The disease is caused by infiltration of allo-activated donor T cells primarily into the gastrointestinal tract and skin. While cytotoxic T cells mediate direct cellular damage, T helper (Th) cells differentially secrete immunoregulatory cytokines. Acute GvHD is thought to be primarily initiated by Th1 cells but a consensus is still lacking regarding the role of Th2 and Th17 cells. The aim of this study was to determine the contribution of distinct T cell subsets to aGvHD in the rat...
February 23, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28238805/pharmacological-inhibition-of-lsd1-and-mtor-reduces-mitochondrial-retention-and-associated-ros-levels-in-the-red-blood-cells-of-sickle-cell-disease
#2
Ramasamy Jagadeeswaran, Benjamin A Vazquez, Muthusamy Thiruppathi, Balaji B Ganesh, Vinzon Ibanez, Shuaiying Cui, James D Engel, Alan M Diamond, Robert E Molokie, Joseph DeSimone, Donald Lavelle, Angela Rivers
Sickle cell disease (SCD), an inherited blood disorder caused by a point mutation that renders hemoglobin susceptible to polymerization when deoxygenated, affects millions of people worldwide. Manifestations of SCD include chronic hemolytic anemia, inflammation, painful vaso-occlusive crises, multisystem organ damage, and reduced life expectancy. Part of SCD pathophysiology is the excessive formation of intracellular reactive oxygen species (ROS) in SCD red blood cells (RBCs) which accelerates their hemolysis...
February 23, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28232234/the-calreticulin-control-of-human-stress-erythropoiesis-is-impaired-by-jak2v617f-in-polycythemia-vera
#3
Mario Falchi, Lilian Varricchio, Fabrizio Martelli, Manuela Marra, Orietta Picconi, Agostino Tafuri, Gabriella Girelli, Vladimir N Uversky, Anna Rita Migliaccio
Calreticulin is a Ca(2+) binding protein that shuttle among cellular compartments with proteins bound to its N/P- domains. The knowledge that activation of the human erythropoietin receptor induces Ca(2+)-fluxes suggested us to investigate the role of calreticulin in human erythropoiesis. By western-blot, erythroblasts generated in-vitro from normal sources and JAK2V617F polycythemia vera (PV) patients expressed robust levels of calreticulin. However, Ca(2+) regulated calreticulin conformation only in normal cells...
February 20, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28189651/the-evolving-view-of-the-hematopoietic-stem-cell-niche
#4
REVIEW
Isabel Beerman, Tiago C Luis, Sofie Singbrant, Cristina Lo Celso, Simon Méndez-Ferrer
Hematopoietic stem cells (HSC) reside in specialized microenvironments known as niches. The niche is essential to support HSC function and to maintain a correct balance between self-renewal and differentiation. Recent advances in defining different mesenchymal and endothelial bone marrow cell populations as well as hematopoietic stem and progenitor cells greatly enhanced our understanding of these niches and of the molecular mechanisms by which they regulate HSC function. In addition to the role in maintaining HSCs homeostasis, the niche has also been implicated in the pathogenesis of blood disorders including hematological malignancies...
February 9, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28185904/chromatin-priming-of-genes-in-development-concepts-mechanisms-and-consequences
#5
REVIEW
Constanze Bonifer, Peter N Cockerill
During ontogeny, cells progress through multiple alternate differentiation states by activating distinct gene regulatory networks. In this review we highlight the important role of chromatin priming in facilitating gene activation during lineage specification and in maintaining an epigenetic memory of previous gene activation. We describe that chromatin priming is part of a hugely diverse repertoire of regulatory mechanisms that genes use to ensure that they are expressed at the correct time, in the correct cell type, at the correct level, but also that they react to signals...
February 6, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28174131/application-of-vitamin-d-and-vitamin-d-analogs-in-acute-myelogenous-leukemia
#6
REVIEW
Huynh Cao, Yi Xu, Rosalia de Necochea-Campion, David J Baylink, Kimberly J Payne, Xiaolei Tang, Christina Ratanatharathorn, Yong Ji, Saied Mirshahidi, Chien-Shing Chen
Acute myeloid leukemia (AML) is characterized by the accumulation of malignant transformed immature hematopoietic myeloid precursors that have lost their ability to differentiate and proliferate normally. Current treatment for acute myeloid leukemia (AML) requires intensive cytotoxic chemotherapy and results in significant morbidity and mortality, especially in older patients. Effective and better-tolerated treatment is urgently needed. Studies have shown that 1α,25-Dihydroxyvitamin D3 (1,25-D3, active VD3) or vitamin D analogs (VDAs) can potently differentiate AML cells in vitro and ex vivo, which led to early clinical trials in AML and myelodysplastic syndrome patients...
February 4, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28167288/impact-of-tet2-deficiency-on-iron-metabolism-in-erythroblasts
#7
Kyoko Inokura, Tohru Fujiwara, Kei Saito, Tatsuya Iino, Shunsuke Hatta, Yoko Okitsu, Noriko Fukuhara, Yasushi Onishi, Kenichi Ishizawa, Kazuya Shimoda, Hideo Harigae
Sideroblastic anemia is characterized by the presence of ring sideroblasts, which are caused by iron accumulation in the mitochondria of erythroblasts and are present in both acquired and congenital forms of sideroblastic anemia. However, the mechanism leading to ring sideroblast formation remains elusive. Acquired sideroblastic anemia is usually observed in myelodysplastic syndrome. Because a subset of myelodysplastic syndrome harbors a somatic mutation of TET2, it may be involved in iron metabolism and/or heme biosynthesis in erythroblasts...
February 3, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28159598/predictive-value-of-pretransplantation-molecular-minimal-residual-disease-assessment-by-wt1-gene-expression-in-flt3-positive-acute-myeloid-leukemia
#8
Anna Candoni, Federico De Marchi, Francesca Zanini, Maria Elena Zannier, Erica Simeone, Eleonora Toffoletti, Alexsia Chiarvesio, Michela Cerno, Carla Filì, Francesca Patriarca, Renato Fanin
The FMS-like tyrosine kinase 3 (FLT3) mutation in acute myeloid leukemia (AML) is a negative prognostic factor and, in these cases, allogeneic stem cell transplantation (allo-SCT) can represent an important therapeutic option, especially if performed in complete remission (CR). However, it is increasingly clear that not all cytological CRs (cCRs) are the same and that minimal residual disease (MRD) before allo-SCT could have an impact on AML outcome. Unfortunately, FLT3, due its instability of expression, is still not considered a good molecular MRD marker...
February 1, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28147232/use-of-ubiquitous-highly-heterozygous-copy-number-variants-and-digital-droplet-pcr-to-monitor-chimerism-after-allogeneic-haematopoietic-stem-cell-transplantation
#9
John B Whitlam, Ling Ling, Michael Swain, Tom Harrington, Oksana Mirochnik, Ian Brooks, Sara Cronin, Jackie Challis, Vida Petrovic, Damien L Bruno, Francoise Mechinaud, Rachel Conyers, Howard Slater
Chimerism analysis has an important role in the management of allogeneic haematopoietic stem cell transplantation. It informs response to disease relapse, graft rejection and graft-versus-host disease. We have developed a method for chimerism analysis using ubiquitous copy number variation (CNV), which has the benefit of a "negative background" against which multiple independent informative markers are absolutely quantified using digital droplet PCR. A panel of up to 38 CNV markers with homozygous deletion frequencies of approximately 0...
January 29, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28115200/androgen-receptor-expression-in-mantle-cell-lymphoma-potential-novel-therapeutic-implications
#10
Elahe A Mostaghel, Paul S Martin, Stephen Mongovin, Shani Frayo, Ailin Zhang, Kerstin L Edlefsen, Oliver W Press, Ajay K Gopal
Mantle cell lymphoma (MCL) affects approximately 4500 patients/year in the US and demonstrates a male to female ratio of approximately 4:1. While the pathobiology underlying this ratio is unknown, the hematopoietic system is characterized by sex-related differences in androgen receptor (AR) expression, leading us to hypothesize that the male-biased incidence of MCL may reflect sex-related differences in AR signaling during MCL lymphomagenesis. To explore the AR axis in MCL, we evaluated AR expression in MCL cell lines and human tumors, and tested the impact of androgen pathway inhibition on MCL proliferation...
January 21, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28087429/analysis-of-parameters-that-affect-human-hematopoietic-cell-outputs-in-mutant-c-kit-immunodeficient-mice
#11
Paul H Miller, Gabrielle Rabu, Margarita MacAldaz, David J H F Knapp, Alice M S Cheung, Kiran Dhillon, Naoto Nakamichi, Philip A Beer, Leonard D Shultz, R Keith Humphries, Connie J Eaves
Xenograft models are transforming our understanding of the output capabilities of primitive human hematopoietic cells in vivo. However, many variables that affect posttransplantation reconstitution dynamics remain poorly understood. Here, we show that an equivalent level of human chimerism can be regenerated from human CD34(+) cord blood cells transplanted intravenously either with or without additional radiation-inactivated cells into 2- to 6-month-old NOD-Rag1(-/-)-IL2Rγc(-/-) (NRG) mice given a more radioprotective conditioning regimen than is possible in conventionally used, repair-deficient NOD-Prkdc(scid/scid)-IL2Rγc(-/-) (NSG) hosts...
January 11, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28087428/polycomb-complexes-prc1-and-their-function-in-hematopoiesis
#12
REVIEW
Miguel Vidal, Katharzina Starowicz
Hematopoiesis, the process by which blood cells are continuously produced, is one of the best studied differentiation pathways. Hematological diseases are associated to reiterated mutations in genes encoding important gene expression regulators, including chromatin regulators. Among them, the Polycomb group (PcG) of proteins is an essential system of gene silencing involved in the maintenance of cell identities during differentiation. PcG proteins assemble into two major types of Polycomb repressive complexes (PRC) endowed with distinct histone tail modifying activities...
January 10, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28062363/governing-roles-for-trib3-pseudokinase-during-stress-erythropoiesis
#13
Arvind Dev, Ruth Asch, Edward Jachimowicz, Nicole Rainville, Ashley Johnson, Emily Greenfest-Allen, Don M Wojchowski
In response to anemia, the heightened production of erythropoietin (EPO) can sharply promote erythroid progenitor cell (EPC) formation. Specific mediators of such EPO- accelerated erythropoiesis, however, are not well understood. Presently, we first report that the expression of Trib3 in adult bone marrow EPCs in vivo is nominal at steady state, but strongly activated on EPO challenge. In a knockout mouse model, Trib3 disruption modestly increased steady-state erythrocyte numbers and decreased mean corpuscular volume...
January 4, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28062362/induced-pluripotent-stem-cell-technology-a-window-for-studying-the-pathogenesis-of-acquired-aplastic-anemia-and-possible-applications
#14
REVIEW
Mahmoud I Elbadry, J Luis Espinoza, Shinji Nakao
Recent progress in human induced pluripotent stem cells (iPSCs) has opened the door to a better understanding of the biology of human diseases, especially rare disorders such as acquired aplastic anemia, in which the target hematopoietic tissues are depleted. The advent of somatic cell reprogramming has presented new routes for generating hematopoietic stem cells from patient-derived iPSCs and their differentiation into hematopoietic lineages. The purpose of this review is to discuss the recent advances in iPSC research technology and their potential applications in disease modeling for understanding the pathogenesis of bone marrow failure syndrome and the potential clinical utility of iPSC-derived cells...
January 3, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28043822/hemangioblast-hemogenic-endothelium-and-primitive-versus-definitive-hematopoiesis
#15
REVIEW
Georges Lacaud, Valerie Kouskoff
The types of progenitors generated during the successive stages of embryonic blood development are now fairly well characterized. The terminology used to describe these waves, however, can still be confusing. What is truly primitive? What is uniquely definitive? These questions become even more challenging to answer when blood progenitors are derived in vitro upon the differentiation of embryonic stem cells or induced pluripotent stem cells. Similarly, the cellular origin of these blood progenitors can be controversial...
December 30, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/28043821/shipping-mouse-bone-marrow-keep-it-in-the-bone
#16
Ani E Papazian, Youmna S Kfoury, David T Scadden
Sharing reagents is of self-evident value in life science research, however, primary cell populations often do not cryopreserve well or can require extensive preparation by collaborators, making shipping difficult. Here we report an evaluation of different conditions for the storage shipment of mouse bone marrow (BM) cells that would best preserve the number, viability, and frequency of different hematopoietic lineages, as well as functionality of progenitor populations. Bones were either crushed to release BM cells or stored intact in one of three media: Phosphate buffered saline (PBS) supplemented with 2% fetal bovine serum (FBS), Plasmalyte, or RPMI at 4°C...
December 30, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/28043820/kinase-signaling-and-targeted-therapy-for-primary-myelofibrosis
#17
REVIEW
Qiong Yang, John D Crispino, Qiang Jeremy Wen
The myeloproliferative neoplasms (MPNs) are somatic mutation-driven hematologic malignancies characterized by bone marrow fibrosis and the accumulation of atypical megakaryocytes with reduced polyploidization in the primary myelofibrosis subtype of the MPNs. Increasing evidence points to a dominant role of abnormal megakaryocytes 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/28034776/letter-to-the-editor-mutational-analysis-of-hypermutation-related-pole-gene-in-acute-leukemias-and-lymphomas
#18
LETTER
Eun Ji Choi, Min Sung Kim, Nam Jin Yoo, Sug Hyung Lee
No abstract text is available yet for this article.
December 26, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/28027963/donor-lymphocyte-infusions-in-aml-and-mds-enhancing-the-graft-versus-leukemia-effect
#19
REVIEW
Guillermo Orti, Pere Barba, Laura Fox, Olga Salamero, Francesc Bosch, David Valcarcel
Allogeneic hematopoietic cell transplantation (allo-HCT) represents the only curative therapy for many haematological malignancies. Its curative potential is mostly attributed to the graft-versus-leukemia effect (GvL), which is mainly driven by donor T-cells. Donor lymphocyte infusions (DLI), likewise a second allo-HCT, have become a standard approach to treat AML and MDS relapses post allo-HCT. Although DLI have been used in this setting for decades, its effectivity and toxicity are still unpredictable in many patients...
December 24, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/28007655/ixazomib-suppresses-human-dendritic-cell-and-modulates-murine-graft-versus-host-disease-in-a-schedule-dependent-fashion
#20
Ahmad Samer Al-Homsi, Austin Goodyke, Kelli Cole, Marlee Muilenburg, Michael McLane, Sarah Abdel-Mageed, Yuxin Feng
There is an abiding need for innovative approaches to the prevention of graft-versus-host disease (GvHD) following allogeneic hematopoietic stem cell transplantation (HSCT). Interest in prevention of GvHD by dendritic cell (DC) suppression has re-emerged since the introduction of proteasome inhibitors into clinical practice. Ixazomib is an orally bioavailable proteasome inhibitor with a rapid proteasome dissociation rate. We studied the effects of ixazomib on human DC maturation, viability, and cytokine production in vitro...
December 19, 2016: Experimental Hematology
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