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https://www.readbyqxmd.com/read/27821476/notch-downregulation-and-extramedullary-erythrocytosis-in-hif-prolyl-4-hydroxylase-2-deficient-mice
#1
Mikko N M Myllymäki, Jenni Määttä, Elitsa Y Dimova, Valerio Izzi, Timo Väisänen, Johanna Myllyharju, Peppi Koivunen, Raisa Serpi
Erythrocytosis is mainly driven by erythropoietin, which is regulated by hypoxia-inducible factor (HIF). Mutations in HIF prolyl 4-hydroxylase 2 (HIF-P4H-2/PHD2/EGLN1), the major downregulator of HIFα subunits, are found in familiar erythrocytosis, and large-spectrum conditional inactivation of HIF-P4H-2 in mice leads to severe erythrocytosis. Although bone marrow is the primary site for erythropoiesis, spleen remains capable for extramedullary erythropoiesis. We studied HIF-P4H-2 deficient mice (Hif-p4h-2(gt/gt)) which show slightly induced erythropoiesis upon aging despite non-increased erythropoietin levels, and identified spleen as the site of extramedullary erythropoiesis...
November 7, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27777239/tgf-%C3%AE-inhibitors-stimulate-red-blood-cell-production-by-enhancing-self-renewal-of-bfu-e-erythroid-progenitors
#2
Xiaofei Gao, Hsiang-Ying Lee, Edroaldo Lummertz da Rocha, Cheng Zhang, Yi-Fen Lu, Dandan Li, Yuxiong Feng, Jideofor Ezike, Russell R Elmes, M Inmaculada Barrasa, Patrick Cahan, Hu Li, George Q Daley, Harvey F Lodish
Burst-forming unit erythroid progenitors (BFU-Es) are so-named based on their ability to generate in methylcellulose culture large colonies of erythroid cells that consist of "bursts" of smaller erythroid colonies derived from the later CFU-E Epo- dependent progenitors. "Early" BFU-E cells forming large BFU-E colonies presumably have higher capacities for self-renewal than do "late" BFU-E forming small colonies but the mechanism underlying this heterogeneity remains unknown. We show that the type III transforming growth factor (TGF)-β receptor (TβRIII) is a marker that distinguishes "early" and "late" BFU-Es...
October 24, 2016: Blood
https://www.readbyqxmd.com/read/27722113/bone-marrow-hematopoietic-stem-cells-behavior-with-or-without-growth-factors-in-trauma-hemorrhagic-shock
#3
Manoj Kumar, Sanjeev Bhoi, Sujata Mohanty, Vineet Kumar Kamal, D N Rao, Pravas Mishra, Sagar Galwankar
BACKGROUND: Hemorrhagic shock (HS) is the major leading cause of death after trauma. Up to 50% of early deaths are due to massive hemorrhage. Excessive release of pro-inflammatory cytokine and hypercatecholamine induces hematopoietic progenitor cells (HPCs) apoptosis, leading to multiorgan failure and death. However, still, result remains elusive for hematopoietic stem cells (HSCs) behavior in trauma HS (T/HS). OBJECTIVES: Therefore, our aim was to evaluate the in vitro HSCs behavior with or without recombinant human erythropoietin (rhEPO), recombinant human granulocyte macrophage-colony-stimulating factor (rhGM-CSF), recombinant human interleukin-3 (rhIL-3) alone, and combination with rhEPO + rhGM-CSF + rhIL-3 (EG3) in T/HS patients...
July 2016: International Journal of Critical Illness and Injury Science
https://www.readbyqxmd.com/read/27553422/parental-origin-of-the-deletion-del-20q-in-shwachman-diamond-patients-and-loss-of-the-paternally-derived-allele-of-the-imprinted-l3mbtl1-gene
#4
Lucia Nacci, Roberto Valli, Rita Maria Pinto, Marco Zecca, Marco Cipolli, Jacopo Morini, Simone Cesaro, Emanuela Boveri, Vittorio Rosti, Paola Corti, Maura Ambroni, Francesco Pasquali, Cesare Danesino, Emanuela Maserati, Antonella Minelli
Shwachman-Diamond syndrome (SDS) (OMIM 260400) is a rare autosomal recessive disease characterized by exocrine pancreatic insufficiency, skeletal, and hematological abnormalities and bone marrow (BM) dysfunction. Mutations in the SBDS gene cause SDS. Clonal chromosome anomalies are often present in BM, i(7)(q10) and del(20q) being the most frequent ones. We collected 6 SDS cases with del(20q): a cluster of imprinted genes, including L3MBTL1 and SGK2 is present in the deleted region. Only the paternal allele is expressed for these genes...
January 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27339418/formaldehyde-induces-toxicity-in-mouse-bone-marrow-and-hematopoietic-stem-progenitor-cells-and-enhances-benzene-induced-adverse-effects
#5
Chenxi Wei, Huaxiao Wen, Langyue Yuan, Cliona M McHale, Hui Li, Kun Wang, Junlin Yuan, Xu Yang, Luoping Zhang
Formaldehyde (FA) is a human leukemogen and is hematotoxic in human and mouse. The biological plausibility of FA-induced leukemia is controversial because few studies have reported FA-induced bone marrow (BM) toxicity, and none have reported BM stem/progenitor cell toxicity. We sought to comprehensively examine FA hematoxicity in vivo in mouse peripheral blood, BM, spleen and myeloid progenitors. We included the leukemogen and BM toxicant, benzene (BZ), as a positive control, separately and together with FA as co-exposure occurs frequently...
June 23, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27268089/adult-human-megakaryocyte-erythroid-progenitors-are-in-the-cd34-cd38mid-fraction
#6
Chad Sanada, Juliana Xavier-Ferrucio, Yi-Chien Lu, Elizabeth Min, Ping-Xia Zhang, Siying Zou, Elaine Kang, Meng Zhang, Gazelle Zerafati, Patrick G Gallagher, Diane S Krause
Bipotent megakaryocyte/erythroid progenitors (MEPs) give rise to progeny limited to the megakaryocyte (Mk) and erythroid (E) lineages. We developed a novel dual-detection functional in vitro colony-forming unit (CFU) assay for single cells that differentiates down both the Mk and E lineages (CFU-Mk/E), which allowed development and validation of a novel purification strategy for the identification and quantitation of primary functional human MEPs from granulocyte colony-stimulating factor-mobilized peripheral blood and bone marrow...
August 18, 2016: Blood
https://www.readbyqxmd.com/read/27114459/a-thrombopoietin-receptor-antagonist-is-capable-of-depleting-myelofibrosis-hematopoietic-stem-and-progenitor-cells
#7
Xiaoli Wang, David Haylock, Cing Siang Hu, Wioleta Kowalczyk, Tianbo Jiang, Jiajing Qiu, Goar Mosoyan, Wu He, Netonia Marshall, John Mascarenhas, Anna Tarasova, Joshua Brody, David Winkler, Ronald Hoffman
Recently, interactions between thrombopoietin (TPO) and its receptor, the myeloproliferative leukemia (MPL) virus oncogene, have been shown to play a role in the development and progression of myeloproliferative neoplasms including myelofibrosis (MF). These observations have led to the development of strategies to disrupt the association of TPO with its receptor as a means of targeting MF hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). In this report, we show that although both splenic and peripheral blood MF CD34(+) cells expressed lower levels of MPL than normal CD34(+) cells, TPO promoted the proliferation of MF CD34(+) cells and HPCs in a dose-dependent fashion...
June 30, 2016: Blood
https://www.readbyqxmd.com/read/27111450/endothelial-cell-selective-adhesion-molecule-expression-in-hematopoietic-stem-progenitor-cells-is-essential-for-erythropoiesis-recovery-after-bone-marrow-injury
#8
Takao Sudo, Takafumi Yokota, Daisuke Okuzaki, Tomoaki Ueda, Michiko Ichii, Tomohiko Ishibashi, Tomomi Isono, Yoko Habuchi, Kenji Oritani, Yuzuru Kanakura
Numerous red blood cells are generated every second from proliferative progenitor cells under a homeostatic state. Increased erythropoietic activity is required after myelo-suppression as a result of chemo-radio therapies. Our previous study revealed that the endothelial cell-selective adhesion molecule (ESAM), an authentic hematopoietic stem cell marker, plays essential roles in stress-induced hematopoiesis. To determine the physiological importance of ESAM in erythroid recovery, ESAM-knockout (KO) mice were treated with the anti-cancer drug, 5-fluorouracil (5-FU)...
2016: PloS One
https://www.readbyqxmd.com/read/27042854/mice-with-a-mutation-in-the-mdm2-gene-that-interferes-with-mdm2-ribosomal-protein-binding-develop-a-defect-in-erythropoiesis
#9
Takuya Kamio, Bai-wei Gu, Timothy S Olson, Yanping Zhang, Philip J Mason, Monica Bessler
MDM2, an E3 ubiquitin ligase, is an important negative regulator of tumor suppressor p53. In turn the Mdm2 gene is a transcriptional target of p53, forming a negative feedback loop that is important in cell cycle control. It has recently become apparent that the ubiquitination of p53 by MDM2 can be inhibited when certain ribosomal proteins, including RPL5 and RPL11, bind to MDM2. This inhibition, and the resulting increase in p53 levels has been proposed to be responsible for the red cell aplasia seen in Diamond-Blackfan anemia (DBA) and in 5q- myelodysplastic syndrome (MDS)...
2016: PloS One
https://www.readbyqxmd.com/read/26913421/-relationship-among-the-oxygen-concentration-reactive-oxygen-species-and-the-biological-characteristics-of-mouse-bone-marrow-hematopoietic-stem-cells
#10
Si-Hua Ren, Yu-Xin He, Yi-Ran Ma, Jing-Chun Jin, Dan Kang
OBJECTIVE: To investigate the effects of oxygen concentration and reactive oxygen species (ROS) on the biological characteristics of hematopoietic stem cells (HSC) and to analyzed the relationship among the oxygen concentration, ROS and the biological characteristics of mouse HSC through simulation of oxygen environment experienced by PB HSC during transplantation. METHODS: The detection of reactive oxygen species (ROS), in vitro amplification, directional differentiation (BFU-E, CFU-GM, CFU-Mix), homing of adhesion molecules (CXCR4, CD44, VLA4, VLA5, P-selectin), migration rate, CFU-S of NOD/SCID mice irradiated with sublethal dose were performed to study the effect of oxgen concentration and reactive oxygen species on the biological characteristics of mouse BM-HSC and the relationship among them...
February 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/26910909/apg101-efficiently-rescues-erythropoiesis-in-lower-risk-myelodysplastic-syndromes-with-severe-impairment-of-hematopoiesis
#11
Anna Raimbault, Cecile Pierre-Eugene, Alexandra Rouquette, Celine Deudon, Lise Willems, Nicolas Chapuis, Stephanie Mathis, Claudia Kunz, Harald Fricke, Olivier Kosmider, Valerie Bardet, Michaela Fontenay
CD95, a member of the death receptor family initiates a caspase-dependent apoptosis, when activated by its ligand CD95L, thought to negatively regulate erythrocyte production in the bone marrow. We have previously shown that CD95 is overexpressed in two thirds of patients with a lower risk myelodysplastic syndrome (MDS) and that resistance to erythropoiesis-stimulating agents (ESA) is linked to poor residual erythropoiesis. In the present study, we show that CD95 overexpression and previous transfusion are independent predictive factors of ESA resistance...
March 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/26801519/hematopoietic-peripheral-circulating-blood-stem-cells-as-an-independent-marker-of-good-transfusion-management-in-patients-with-%C3%AE-thalassemia-results-from-a-preliminary-study
#12
Mariasanta Napolitano, Calogera Gerardi, Anna Di Lucia, Pietro Andrea Accardo, Luigi Rizzuto, Maria Ferraro, Sergio Siragusa, Filippo Buscemi
BACKGROUND: Beyond hemoglobin (Hb) levels and performance status, further surrogate markers of appropriate transfusion management should improve the quality of thalassemia care. We investigated the levels of peripheral circulating CD34+ stem cells as an independent marker of appropriate hematopoietic balance in patients with thalassemia. STUDY DESIGN AND METHODS: Peripheral circulating CD34+ stem cells, colony-forming unitgranulocyte, erythrocyte, macrophage, magakaryocyte (CF-GEMM), colony-forming unitgranulocyte/macrophage (CFU-GM), and erythroidburst-forming units (BFU-E) were assayed, according to standard procedures...
April 2016: Transfusion
https://www.readbyqxmd.com/read/26679864/pomalidomide-reverses-%C3%AE-globin-silencing-through-the-transcriptional-reprogramming-of-adult-hematopoietic-progenitors
#13
Brian M Dulmovits, Abena O Appiah-Kubi, Julien Papoin, John Hale, Mingzhu He, Yousef Al-Abed, Sebastien Didier, Michael Gould, Sehba Husain-Krautter, Sharon A Singh, Kyle W H Chan, Adrianna Vlachos, Steven L Allen, Naomi Taylor, Philippe Marambaud, Xiuli An, Patrick G Gallagher, Narla Mohandas, Jeffrey M Lipton, Johnson M Liu, Lionel Blanc
Current therapeutic strategies for sickle cell anemia are aimed at reactivating fetal hemoglobin. Pomalidomide, a third-generation immunomodulatory drug, was proposed to induce fetal hemoglobin production by an unknown mechanism. Here, we report that pomalidomide induced a fetal-like erythroid differentiation program, leading to a reversion of γ-globin silencing in adult human erythroblasts. Pomalidomide acted early by transiently delaying erythropoiesis at the burst-forming unit-erythroid/colony-forming unit-erythroid transition, but without affecting terminal differentiation...
March 17, 2016: Blood
https://www.readbyqxmd.com/read/26646992/tracking-erythroid-progenitor-cells-in-times-of-need-and-times-of-plenty
#14
REVIEW
Mark J Koury
Red blood cell production rates increase rapidly following blood loss or hemolysis, but the expansion of erythropoiesis in these anemic states is tightly regulated such that rebound polycythemia does not occur. The erythroid cells that respond to erythropoietic stimulation or suppression are the progenitor stages of burst-forming units-erythroid (BFU-Es) and colony-forming units-erythroid (CFU-Es). Results from an early study of the changes in the size, location, and cell cycling status of BFU-E and CFU-E populations in mice under normal conditions, erythropoietic stimulation, and erythropoietic suppression are used as reference points to review subsequent developments related to erythroid progenitor populations and regulation of their size...
August 2016: Experimental Hematology
https://www.readbyqxmd.com/read/26417990/preterm-cord-blood-contains-a-higher-proportion-of-immature-hematopoietic-progenitors-compared-to-term-samples
#15
COMPARATIVE STUDY
Marina Podestà, Matteo Bruschettini, Claudia Cossu, Federica Sabatini, Monica Dagnino, Olga Romantsik, Grazia Maria Spaggiari, Luca Antonio Ramenghi, Francesco Frassoni
BACKGROUND: Cord blood contains high number of hematopoietic cells that after birth disappear. In this paper we have studied the functional properties of the umbilical cord blood progenitor cells collected from term and preterm neonates to establish whether quantitative and/or qualitative differences exist between the two groups. METHODS AND RESULTS: Our results indicate that the percentage of total CD34+ cells was significantly higher in preterm infants compared to full term: 0...
2015: PloS One
https://www.readbyqxmd.com/read/26262635/altered-expression-of-genes-in-signaling-pathways-regulating-proliferation-of-hematopoietic-stem-and-progenitor-cells-in-mice-with-subchronic-benzene-exposure
#16
Rongli Sun, Juan Zhang, Mengzhen Xiong, Haiyan Wei, Kehong Tan, Lihong Yin, Yuepu Pu
Leukemias and hematopoietic disorders induced by benzene may arise from the toxicity of benzene to hematopoietic stem or progenitor cells (HS/PCs). Since there is a latency period between initial benzene exposure and the development of leukemia, subsequent impact of benzene on HS/PCs are crucial for a deeper understanding of the carcinogenicity and hematotoxicity in post-exposure stage. This study aims to explore the effects of benzene on HS/PCs and gene-expression in Wnt, Notch and Hh signaling pathways in post-exposure stage...
August 2015: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/26235290/diamond-blackfan-anemia-death-by-heme-toxicity
#17
EDITORIAL
M Tarek Elghetany
No abstract text is available yet for this article.
April 2016: European Journal of Haematology
https://www.readbyqxmd.com/read/26186557/peripheral-blood-cells-from-children-with-rasopathies-show-enhanced-spontaneous-colonies-growth-in-vitro-and-hyperactive-ras-signaling
#18
G Gaipa, C Bugarin, P Cianci, J Sarno, P Bonaccorso, A Biondi, A Selicorni
Germline mutations in genes coding for molecules involved in the RAS/RAF/MEK/ERK pathway are the hallmarks of a newly classified family of autosomal dominant syndromes termed RASopathies. Myeloproliferative disorders (MPDs), in particular, juvenile myelomonocytic leukemia, can lead to potentially severe complications in children with Noonan syndrome (NS). We studied 27 children with NS or other RASopathies and 35 age-matched children as control subjects. Peripheral blood (PB) cells from these patients were studied for in vitro colony-forming units (CFUs) activity, as well as for intracellular phosphosignaling...
2015: Blood Cancer Journal
https://www.readbyqxmd.com/read/26111997/exploring-erythropoiesis-of-common-carp-cyprinus-carpio-using-an-in-vitro-colony-assay-in-the-presence-of-recombinant-carp-kit-ligand-a-and-erythropoietin
#19
Fumihiko Katakura, Takeshi Yabu, Takuya Yamaguchi, Jiro Miyamae, Yuki Shirinashihama, Teruyuki Nakanishi, Tadaaki Moritomo
The use of in vitro colony assays in mammals has contributed to identification of erythroid progenitor cells such as burst-forming unit-erythroid (BFU-E) and colony-forming unit-erythroid (CFU-E) progenitors, and serves to examine functions of erythropoietic growth factors like Erythropoietin (Epo) and Kit ligand. Here, we established an in vitro colony-forming assay capable of investigating erythropoiesis in carp (Cyprinus carpio), cloned and functionally characterized recombinant homologous molecules Epo and Kit ligand A (Kitla), and identified three distinct erythroid progenitor cells in carp...
November 2015: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/26102347/loss-of-ikk%C3%AE-but-not-nf-%C3%AE%C2%BAb-p65-skews-differentiation-towards-myeloid-over-erythroid-commitment-and-increases-myeloid-progenitor-self-renewal-and-functional-long-term-hematopoietic-stem-cells
#20
Jing Zhang, Li Li, Albert S Baldwin, Alan D Friedman, Ido Paz-Priel
NF-κB is an important regulator of both differentiation and function of lineage-committed hematopoietic cells. Targeted deletion of IκB kinase (IKK) β results in altered cytokine signaling and marked neutrophilia. To investigate the role of IKKβ in regulation of hematopoiesis, we employed Mx1-Cre mediated IKKβ conditional knockout mice. As previously reported, deletion of IKKβ in hematopoietic cells results in neutrophilia, and we now also noted decreased monocytes and modest anemia. Granulocyte-macrophage progenitors (GMPs) accumulated markedly in bone marrow of IKKβ deleted mice whereas the proportion and number of megakaryocyte-erythrocyte progenitors (MEP) decreased...
2015: PloS One
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