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Chenxi Wei, Mouying Chen, Huihui You, Feng Qiu, Huaxiao Wen, Junlin Yuan, Shuanglin Xiang, Xu Yang
Formaldehyde (FA) is a human leukemogen. Since there is a latency period between initial FA exposure and the development of leukemia, the subsequent impact of FA on hematopoietic stem or progenitor cells (HSCs/HPCs) in post-exposure stage is crucial for a deep understanding of FA-induced hematotoxicity. BALB/c mice were exposed to 3mg/m(3) FA for 2weeks, mimicking occupational exposure, and were monitored for another 7days post-exposure. Meanwhile, we included benzene (BZ) as a positive control, separately and together with FA because co-exposure occurs frequently...
June 1, 2017: Toxicology and Applied Pharmacology
Sebastian Medina, Huan Xu, Shu Chun Wang, Fredine T Lauer, Ke Jian Liu, Scott W Burchiel
Epidemiological studies report an association between chronic arsenic (As) exposure and anemia in men, and women who are predisposed to anemia. The purpose of these studies was to determine whether a 60 d drinking water exposure of adult male C57BL/6J mice to 0, 100, and 500ppb arsenite (As(+3)) results in anemia due to alterations in erythroid progenitor cell development in the bone marrow. Exposure to 500ppb As(+3) for 60 d resulted in a reduction of mean corpuscular hemoglobin (MCH) levels, but did not significantly alter red blood cell (RBC) counts, hemoglobin (Hgb) levels, mean corpuscular Hgb concentrations (MCHC), or mean corpuscular volumes (MCV)...
March 27, 2017: Toxicology Letters
Simone Perucca, Andrea Di Palma, Pier Paolo Piccaluga, Claudia Gemelli, Elisa Zoratti, Giulio Bassi, Edoardo Giacopuzzi, Andrea Lojacono, Giuseppe Borsani, Enrico Tagliafico, Maria Teresa Scupoli, Simona Bernardi, Camilla Zanaglio, Federica Cattina, Valeria Cancelli, Michele Malagola, Mauro Krampera, Mirella Marini, Camillo Almici, Sergio Ferrari, Domenico Russo
A human bone marrow-derived mesenchymal stromal cell (MSCs) and cord blood-derived CD34+ stem cell co-culture system was set up in order to evaluate the proliferative and differentiative effects induced by MSCs on CD34+ stem cells, and the reciprocal influences on gene expression profiles. After 10 days of co-culture, non-adherent (SN-fraction) and adherent (AD-fraction) CD34+ stem cells were collected and analysed separately. In the presence of MSCs, a significant increase in CD34+ cell number was observed (fold increase = 14...
2017: PloS One
Hua-Ching Chang, Duen-Yi Huang, Mai-Szu Wu, Ching-Liang Chu, Shiang-Jong Tzeng, Wan-Wan Lin
Erythropoietin (EPO) and GM-CSF are involved in erythropoiesis, while TGF-β inhibits proliferation but potentiates differentiation of erythroblasts. Since Syk inhibitor may induce anemia side effect in clinic, here we investigated the role of Syk in the biological actions of EPO and GM-CSF in erythropoiesis. In human erythroleukemia cell line TF-1, Syk inhibitor R406 exerts an enhancement effect with TGF-β to decrease cell viability, either in the absence or presence of EPO or GM-CSF. Such effect of R406 results from the reduced cell cycle progression and increased cell apoptosis...
April 2017: Biochimica et Biophysica Acta
Ines G Alamo, Kolenkode B Kannan, Letitia E Bible, Tyler J Loftus, Harry Ramos, Philip A Efron, Alicia M Mohr
BACKGROUND: After severe trauma, patients develop a norepinephrine-mediated persistent, injury-associated anemia. This anemia is associated with suppression of bone marrow (BM) erythroid colony growth, along with decreased iron levels, and elevated erythropoietin (EPO) levels, which are insufficient to promote effective erythropoiesis. The impact of norepinephrine on iron regulators, such as ferroportin, transferrin, and transferrin receptor-1 (TFR-1), is unknown. Using a clinically relevant rodent model of lung contusion (LC), hemorrhagic shock (HS), and chronic stress (CS), we hypothesize that daily propranolol (BB), a nonselective β blocker, restores BM function and improves iron homeostasis...
April 2017: Journal of Trauma and Acute Care Surgery
E A Eksioglu, X Chen, K-H Heider, B Rueter, K L McGraw, A A Basiorka, M Wei, A Burnette, P Cheng, J Lancet, R Komrokji, J Djeu, A List, S Wei
We recently reported that the accumulation of myeloid-derived suppressor cells (MDSC), defined as CD33(+)HLA-DR(-)Lin(-), plays a direct role in the pathogenesis of myelodysplastic syndrome (MDS). In particular, CD33 is strongly expressed in MDSC isolated from patients with MDS where it plays an important role in MDSC-mediated hematopoietic suppressive function through its activation by S100A9. Therefore, we tested whether blocking this interaction with a fully human, Fc-engineered monoclonal antibody against CD33 (BI 836858) suppresses CD33-mediated signal transduction and improves the bone marrow microenvironment in MDS...
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Emine Begüm Gencer, Pınar Yurdakul, Klara Dalva, Meral Beksac
OBJECTIVE: Colony forming unit-granulocyte macrophage (CFU-GM) analysis is the most widely used method to determine hematopoieticstem cell (HSC) content of human umbilical cord blood (CB) for prediction of engraftment potential. Measurement of aldehyde dehydrogenase (ALDH) activity is a more recent method for HSC qualification. Our aim was to correlate phenotypic with functional assays to find the most predictive method. MATERIALS AND METHODS: In this study, flow cytometric quantitation of CD34+ cells and ALDH positivity along with CFU-GM capacity were assessed in fresh and post thaw CB units...
December 12, 2016: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Mikko N M Myllymäki, Jenni Määttä, Elitsa Y Dimova, Valerio Izzi, Timo Väisänen, Johanna Myllyharju, Peppi Koivunen, Raisa Serpi
Erythrocytosis is driven mainly 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 of extramedullary erythropoiesis. We studied HIF-P4H-2-deficient (Hif-p4h-2(gt/gt)) mice, which show slightly induced erythropoiesis upon aging despite nonincreased erythropoietin levels, and identified spleen as the site of extramedullary erythropoiesis...
January 15, 2017: Molecular and Cellular Biology
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 colony-forming unit erythroid progenitor erythropoietin (Epo)-dependent progenitors. "Early" BFU-E cells forming large BFU-E colonies presumably have higher capacities for self-renewal than do "late" BFU-Es forming small colonies, but the mechanism underlying this heterogeneity remains unknown...
December 8, 2016: Blood
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
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
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...
February 2017: Archives of Toxicology
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
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
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
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
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
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
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
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
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