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Experimental Hematology

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https://www.readbyqxmd.com/read/28087429/analysis-of-parameters-that-affect-human-hematopoietic-cell-outputs-in-mutant-c-kit-immunodeficient-mice
#1
Paul H Miller, Gabrielle Rabu, Margarita MacAldaz, David Jhf Knapp, Alice Ms 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 post-transplant reconstitution dynamics remain poorly understood. Here we show 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 2-6 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 10, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28087428/polycomb-complexes-prc1-and-their-function-in-hematopoiesis
#2
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
#3
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 upon EPO challenge. In a knockout mouse model, Trib3 disruption modestly decreased steady-state erythrocyte numbers, and increased mean corpuscular volume...
January 3, 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
#4
REVIEW
Mahmoud Elbadry, J Luis Espinoza, Shinji Nakao
Recent progress in human induced pluripotent stem cells (iPSCs) has opened the door to better understand the biology of human diseases, especially in rare disorders, such as acquired aplastic anemia (AA), in which the target hematopoietic tissues are depleted. The advent of somatic cell reprogramming has presented new routes for generating hematopoietic stem cells (HSCs) 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 its potential applications in disease modeling for understanding the pathogenesis of bone marrow failure syndrome (BMFS) and the potential clinical utility of iPSC-derived cells...
January 3, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28043822/of-hemangioblast-hemogenic-endothelium-and-primitive-versus-definitive-hematopoiesis
#5
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 (ESCs) or induced pluripotent stem cells (iPSCs). 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
#6
Ani E Papazian, Youmna S Kfoury, David T Scadden
No abstract text is available yet for this article.
December 30, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/28043820/kinase-signaling-and-targeted-therapy-for-primary-myelofibrosis
#7
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/28034776/letter-to-the-editor-mutational-analysis-of-hypermutation-related-pole-gene-in-acute-leukemias-and-lymphomas
#8
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
#9
REVIEW
G Orti, P Barba, L Fox, O Salamero, F Bosch, D Valcarcel
No abstract text is available yet for this article.
December 24, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/28017647/preclinical-approaches-in-cml-from-cells-to-systems
#10
REVIEW
Cassie J Clarke, Tessa L Holyoake
Advances in the design of targeted therapies for the treatment of chronic myeloid leukaemia (CML) have transformed the prognosis for patients diagnosed with this disease. However, leukemic stem cell persistence, drug intolerance, drug resistance and advanced phase disease, represent unmet clinical needs demanding the attention of CML investigators worldwide. The availability of appropriate preclinical models is essential to efficiently translate findings from the bench to the clinic. Here we review the current approaches taken to preclinical work in the CML field, including examples of commonly used in vivo models and recent successes from systems biology based methodologies...
December 22, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/28017646/targeting-the-transcription-factor-myb-by-small-molecule-inhibitors
#11
REVIEW
Sagar Uttarkar, Jon Frampton, Karl-Heinz Klempnauer
The transcription factor Myb is a key regulator of hematopoietic cell proliferation, differentiation, and survival and has been implicated in the development of leukemia and several other human cancers. Pharmacological inhibition of Myb is therefore emerging as a potential therapeutic strategy. Recently, the first low-molecular-weight compounds that show Myb inhibitory activity have been identified. Characterization of these compounds suggests disruption of the protein-protein-interaction of Myb and the coactivator p300 as a suitable strategy to inhibit Myb...
December 23, 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
#12
A Samer Al-Homsi, Austin Goodyke, Kelli Cole, Marlee Muilenburg, Michael McLane, Sarah Abdel-Mageed, Yuxin Feng
There is an abiding need for innovative approaches for the prevention of graft-versus-host disease (GvHD) following allogeneic hematopoietic stem cell transplantation (HSCT). The interest in dendritic cell (DC) suppression to prevent GvHD has re-emerged since the introduction of proteasome inhibitors into clinical practice. Ixazomib is an orally bioavailable proteasome inhibitor with 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
https://www.readbyqxmd.com/read/27988259/epha5-and-epha7-forward-signalling-enhances-human-hematopoietic-stem-and-progenitor-cell-maintenance-migration-and-adhesion-via-rac1-activation
#13
Thao M Nguyen, Agnieszka Arthur, Andrew C W Zannettino, Stan Gronthos
The proliferation, differentiation, adhesion and migration of hematopoietic stem and progenitor cells (HSPC) are dependent upon bone marrow stromal cells (BMSC). In this study, we found that human primitive HSPC (CD34(+)CD38(-)), but not by lineage committed hematopoietic cell populations, express the tyrosine kinase receptors, EphA5 and EphA7. Moreover, we found that the ephrinA5 ligand, the high affinity binding partner of EphA5 and EphA7, is highly expressed by primary human BMSC. Previous studies have reported that interactions between EphA and ephrinA play important roles in hematopoietic cell trafficking, however their role in BMSC support of hematopoiesis had not been described...
December 14, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27931853/from-the-bedside-to-the-bench-new-discoveries-on-blood-cell-fate-and-function
#14
REVIEW
Eirini Trompouki, Eugenia Flores-Figueroa, Daniel Lucas, Teresa Bowman
Controversy and context: two words that exemplified this year's International Society for Experimental Hematology meeting. Leaders in the field of hematology from around the world gathered in San Diego in August of 2016 to discuss cutting-edge research on diverse topics such as hemoglobin switching, hematopoietic stem cell emergence, leukemogenesis, and aging. Major questions discussed included the "when, where, and how" of hematopoietic emergence, bone marrow residence, and disease origination. This meeting summary covers some of the conference highlights...
December 5, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27931852/the-baf45a-phf10-subunit-of-swi-snf-like-chromatin-remodeling-complexes-is-essential-for-hematopoietic-stem-cell-maintenance
#15
Veneta Krasteva, Gerald R Crabtree, Julie A Lessard
The ability of hemopoietic stem cells to self-renew and differentiate into downstream lineages is dependent on specialized chromatin environments that establish and maintain stage-specific patterns of gene expression. However, the epigenetic factors responsible for mediating these regulatory events remain poorly defined. Here we provide evidence that BAF45a/PHF10, a subunit of SWI/SNF-like chromatin remodeling complexes, is essential for adult hemopoietic stem cell (HSC) maintenance and myeloid lineage development...
December 5, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27915139/impairment-of-fetal-hematopoietic-stem-cell-function-in-the-absence-of-fancd2
#16
Sakiko Suzuki, Ronny R Racine, Nathan A Manalo, Sharon B Cantor, Glen D Raffel
Fanconi anemia (FA) results from mutations in the genes necessary for DNA damage repair and often leads to progressive bone marrow failure. Although the exhaustion of the bone marrow leads to cytopenias in FA patients as they age, evidence from human FA and mouse model fetal livers suggests that hematopoietic defects originate in utero, which may lead to deficient seeding of the bone marrow. To address this possibility, we examined the consequences of loss of Fancd2, a central component of the FA pathway. Examination of embryonic day 14...
December 1, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27889516/lenalidomide-enhances-the-function-of-dendritic-cells-generated-from-patients-with-multiple-myeloma
#17
Manh-Cuong Vo, Truc Anh-NguyenThi, Hyun-Ju Lee, Thanh-Nhan Nguyen-Pham, Thangaraj Jaya Lakshmi, Sung-Hoon Jung, Hyeoung-Joon Kim, Je-Jung Lee
Lenalidomide (LEN) has been used as an immunomodulatory drug with direct and indirect anti-tumor effects. In this study, we evaluated the effect of LEN on the differentiation, maturation, and function of dendritic cells (DCs) in patients with multiple myeloma in vitro. Various doses of LEN were added after the monocytes had differentiated into immature DCs and were activated into mature DCs. LEN (5 μg/mL) was the optimal concentration to promote differentiation and maturation of DCs. Immature DCs treated with LEN exhibited enhanced endocytic capacity...
November 23, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27865805/transcriptional-activation-by-mll-fusion-proteins-in-leukemogenesis
#18
REVIEW
Akihiko Yokoyama
Chromosomal translocations involving the mixed lineage leukemia (MLL) gene cause aggressive leukemia. Fusion proteins of MLL and a component of the AF4 family/ENL family/P-TEFb complex (AEP) are responsible for two-thirds of MLL-associated leukemia cases. MLL-AEP fusion proteins trigger aberrant self-renewal of hematopoietic progenitors by constitutively activating self-renewal-related genes. MLL-AEP fusion proteins activate transcription initiation by loading the TATA-binding protein (TBP) to the TATA element via selectivity factor 1...
November 16, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27864153/immunogenicity-of-murine-mpeg-red-blood-cells-and-the-risk-of-anti-peg-antibodies-in-human-blood-donors
#19
Yevgeniya Le, Wendy M Toyofuku, Mark D Scott
The immunocamouflage of non-ABO blood group antigens by membrane-grafted methoxypoly(ethylene glycol) (mPEG) may attenuate the risk of red blood cell (RBC) alloimmunization. However, concerns have been raised over the immunogenic risk of PEG and PEG-RBCs. To assess this risk, murine and human studies were performed. Mice were exposed to soluble PEG prior to, or between, multiple transfusions (∼60-day intervals) of control or mPEG-RBCs, and cell survival was determined by flow cytometry. In some studies, the control and mPEG-RBC groups were reversed after one or more transfusions...
November 15, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27856324/mll-af4-binds-directly-to-a-bcl-2-specific-enhancer-and-modulates-h3k27%C3%A2-acetylation
#20
Laura Godfrey, Jon Kerry, Ross Thorne, Emmanouela Repapi, James O J Davies, Marta Tapia, Erica Ballabio, Jim R Hughes, Huimin Geng, Marina Konopleva, Thomas A Milne
Survival rates for children and adults carrying mutations in the Mixed Lineage Leukemia (MLL) gene continue to have a very poor prognosis. The most common MLL mutation in acute lymphoblastic leukemia is the t(4;11)(q21;q23) chromosome translocation that fuses MLL in-frame with the AF4 gene producing MLL-AF4 and AF4-MLL fusion proteins. Previously, we found that MLL-AF4 binds to the BCL-2 gene and directly activates it through DOT1L recruitment and increased H3K79me2/3 levels. In the study described here, we performed a detailed analysis of MLL-AF4 regulation of the entire BCL-2 family...
November 14, 2016: Experimental Hematology
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