Abstract:
:Fetal hemoglobin (HbF) is a potent genetic modifier of the severity of beta-thalassemia and sickle cell anemia. We used an in vitro culture model of human erythropoiesis in which late-stage erythroblasts are derived directly from human CD34(+) hematopoietic cells to evaluate HbF production. This system recapitulates expression of globin genes according to the developmental stage of the originating cell source. When cytokine-mobilized peripheral blood CD34(+) cells from adults were cultured, background levels of HbF were 2% or less. Cultured cells were readily transduced with lentiviral vectors when exposed to vector particles between 48 and 72 hours. Among the genetic elements that may enhance fetal hemoglobin production is an artificial zinc-finger transcription factor, GG1-VP64, designed to interact with the proximal gamma-globin gene promoters. Our data show that lentiviral-mediated, enforced expression of GG1-VP64 under the control of relatively weak erythroid-specific promoters induced significant amounts of HbF (up to 20%) in erythroblasts derived from adult CD34(+) cells without altering their capacity for erythroid maturation and only modestly reducing the total numbers of cells that accumulate in culture after transduction. These observations demonstrate the potential for sequence-specific enhancement of HbF in patients with beta-thalassemia or sickle cell anemia.
journal_name
Bloodjournal_title
Bloodauthors
Wilber A,Tschulena U,Hargrove PW,Kim YS,Persons DA,Barbas CF 3rd,Nienhuis AWdoi
10.1182/blood-2009-08-240556subject
Has Abstractpub_date
2010-04-15 00:00:00pages
3033-41issue
15eissn
0006-4971issn
1528-0020pii
blood-2009-08-240556journal_volume
115pub_type
杂志文章相关文献
BLOOD文献大全abstract::The interaction of von Willebrand factor (vWF) with the alpha v beta 3 integrin of human umbilical vein endothelial cells is dependent on the RGD sequence present at residues 1744-1746 of the mature vWF subunit. We compared vWF and its two dimeric fragments, SpIII (residues 1-1365) and SpII (residues 1366-2050), as ad...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-12-15 00:00:00
abstract::Inflammatory responses represent a hallmark of numerous pathologies including sepsis, bacterial infection, insulin resistance, and malign obesity. Here we describe an unexpected coactivator function for the nuclear receptor interacting protein 140 (RIP140) for nuclear factor kappaB (NFkappaB), a master transcriptional...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-11-121699
更新日期:2008-07-15 00:00:00
abstract::Protein S, an inhibitor of coagulation, interacts reversibly with C4b binding protein (C4bBP). The physiologic role of this complex formation remains unknown. In this study we examined the possibility that protein S would facilitate C4bBP binding to the surface of neutrophils where, in turn, this complex could help pr...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-01-15 00:00:00
abstract::To understand the hematopoietic and nonhematopoietic responses to interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was examined on bone marrow (BM) cells and peripheral blood (PB) cells of rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R expression is low in untreated mo...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-07-15 00:00:00
abstract::GVHD is still one of the major complications after allogeneic stem cell transplantation. Whereas murine data have clearly shown the beneficial effects of regulatory T cells (Tregs) on the prevention of GVHD, data from the human system are rare. Here, we present a comparative dynamic analysis of CD4(+)CD25(hi)CD127(lo/...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-05-352708
更新日期:2011-09-29 00:00:00
abstract::Current dosing algorithms do not account for genetic and environmental factors for warfarin dose determinations. This study investigated the contribution of age, CYP2C9 and VKORC1 genotype, and body size to warfarin-dose requirements. Studied were 297 patients with stable anticoagulation with a target international no...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-03-1108
更新日期:2005-10-01 00:00:00
abstract::The monoclonal antibodies Tab and AP3 are directed, respectively, against GPIIb and GPIIIa, the subunits of the platelet fibrinogen receptor. When added together to platelets, these antibodies prevent adenosine diphosphate (ADP)-induced platelet aggregation, despite normal fibrinogen binding (Newman et al, Blood 69:66...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-10-15 00:00:00
abstract::Human bone marrow (BM) cells contain low levels of the DNA repair protein, O6-alkylguanine-DNA alkyltransferase, which may explain their susceptibility to nitrosourea-induced cytotoxicity and the development of secondary leukemia after nitrosourea treatment. Isolated CD34+ myeloid progenitors were also found to have l...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::In this issue of Blood, Savona and an international consortium of clinical investigators propose uniform response criteria for treatment trials enrolling adult patients with myelodysplastic/myeloproliferative neoplasms (MDS/MPNs). Such a proposal is needed because new drugs are finally being tested in these rare “over...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2015-02-626473
更新日期:2015-03-19 00:00:00
abstract::A prominent feature of sickle cell anemia is the presence of dehydrated red blood cells (RBCs) in circulation. Loss of potassium (K(+)), chloride (Cl(-)), and water from RBCs is thought to contribute to the production of these dehydrated cells. One main route of K(+) loss in the RBC is the Gardos channel, a calcium (C...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-05-1433
更新日期:2003-03-15 00:00:00
abstract::Until recently, the identification of cellular factors that govern the developmental program of human stem cells has been difficult due to the absence of repopulation assays that detect human stem cells. The transplantation of human bone marrow (BM) or cord blood (CB) into non-obese diabetic (NOD)/severe-combined immu...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-09-15 00:00:00
abstract::Fanconi anemia (FA) is an autosomal recessive syndrome characterized by progressive bone marrow failure and cancer predisposition. Eight FA complementation groups have been identified. The FANCA, FANCC, FANCE, FANCF, and FANCG proteins form a nuclear complex required for the monoubiquination of the FANCD2 protein. To ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-11-3517
更新日期:2003-07-01 00:00:00
abstract::The stage of progenitor maturation and factors that determine the fate and clonal acquisition of human natural killer (NK) cell receptors during development are unknown. To study human NK cell receptor ontogeny, umbilical cord blood CD34(+)/Lin(-)/CD38(-) cells were cultured with a murine fetal liver line (AFT024) and...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v98.3.705
更新日期:2001-08-01 00:00:00
abstract::In this issue of Blood, Baychelier et al identify a ligand for a major natural killer (NK) cell receptor that mediates natural cytotoxicity toward tumor cells, thus ending a search that lasted well over a decade. ...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2013-09-523696
更新日期:2013-10-24 00:00:00
abstract::Immunosuppression resulting in impaired Epstein-Barr virus (EBV)-specific T-cell immunity is involved in the pathogenesis of EBV-positive post-transplantation lymphoproliferative disorder (EBV(+) PTLD). Restoration of EBV-specific T-cell immunity by adoptive immunotherapy can induce remission. EBV-nuclear antigen-1 (E...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-03-274076
更新日期:2010-09-30 00:00:00
abstract::In 21 patients with lymphoproliferative disease of granular lymphocytes (LDGL), we investigated the expression and the function of molecules belonging to TNF-receptor and TNF-ligand superfamilies (CD30/CD30L; CD40/CD40L; CD27/CD70; Fas [CD95]/FasL[CD95L]). Fourteen patients were characterized by a proliferation of gra...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-07-15 00:00:00
abstract::Recent molecular analyses of leukemic blasts from pretreatment marrow or blood of patients with acute myeloid leukemia (AML) and a normal karyotype, the largest cytogenetic subset (ie, 40%-49%) of AML, have revealed a striking heterogeneity with regard to the presence of acquired gene mutations and changes in gene exp...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2006-06-001149
更新日期:2007-01-15 00:00:00
abstract::Low-grade follicular non-Hodgkin's lymphomas are characterized by the presence of a t(14;18) chromosomal translocation that results in deregulation of the B-cell lymphoma (Bcl-2) gene. Studies in cell lines and transgenic animal models have suggested that this results in the suppression of apoptotic cell death in germ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-09-15 00:00:00
abstract::Polycythemia vera (PV) treatment with interferon α (IFNα) is frequently limited by dose-related toxicity. PV CD34(+) cells are characterized by overexpression of Bcl-xL, which can be antagonized by ABT-737 leading to apoptosis. We explored the effects of ABT-737 and IFNα on PV hematopoiesis. Both IFNα and ABT-737 alon...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-04-279125
更新日期:2010-11-18 00:00:00
abstract::Anemia and neutropenia often develop in cats that are infected with the feline immunodeficiency virus (FIV), a lentivirus biologically similar to the human immunodeficiency virus (HIV). To assess the role of FIV in the pathogenesis of these abnormalities, marrow culture studies were performed on nine asymptomatic, hem...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-10-15 00:00:00
abstract::A new type of A alpha Glu-11 to Gly substitution has been identified in a congenitally abnormal fibrinogen, fibrinogen Mitaka II, derived from a 14-year-old female suffering from easy bruising since childhood. Plasma of the patient and fibrinogen purified therefrom were found to clot slowly by thrombin but in a normal...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-12-15 00:00:00
abstract::One hundred fifty-one children with acute myelogenous leukemia (AML) entered the cooperative study BFM-78 between December 1978 and October 1982. The initial therapy consisted of an intensive induction and consolidation regimen over eight weeks with seven different drugs and cranial irradiation. It was followed by mai...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::Recent population-based studies demonstrate an increased fracture risk with monoclonal gammopathy of undetermined significance (MGUS). The etiology of this increased risk remains unclear, however, because areal bone mineral density (aBMD) measurements by dual-energy x-ray absorptiometry cannot assess bone microstructu...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-04-351437
更新日期:2011-12-15 00:00:00
abstract::Nitric oxide (NO) exerts vasodilatatory, antiplatelet, antioxidant, and antiproliferative effects. Endothelium-derived NO has been shown to be of crucial importance in cardiovascular protection, whereas evidence that NO is synthesized by platelets and regulates platelet function is still controversial. By using a sens...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-06-579474
更新日期:2015-01-22 00:00:00
abstract::Pyrimidine 5' nucleotidase (P5'N-1) deficiency is an autosomal recessive condition causing hemolytic anemia characterized by marked basophilic stippling and the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. It is implicated in the anemia of lead poisoning and is possibly associa...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v97.11.3327
更新日期:2001-06-01 00:00:00
abstract::In vitro studies suggest that Ras activation is necessary for erythroid cell development. However, genetic inactivation of the Ras isoforms H-Ras, N-Ras, and K-Ras in mice reportedly did not affect adult or fetal erythropoiesis, though K-Ras(-/-) embryos were anemic. Given these discrepancies, we performed a more deta...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-05-2021
更新日期:2005-05-01 00:00:00
abstract::Induction of red blood cell (RBC) fetal hemoglobin (HbF; α2γ2) ameliorates the pathophysiology of sickle cell disease (SCD) by reducing the concentration of sickle hemoglobin (HbS; α2βS2) to inhibit its polymerization. Hydroxyurea (HU), the only US Food and Drug Administration (FDA)-approved drug for SCD, acts in part...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2017-11-814335
更新日期:2018-07-19 00:00:00
abstract::The response of megakaryocytes and platelets to the administration of recombinant human interleukin-6 (IL-6) was investigated in normal and sublethally irradiated dogs. IL-6 was administered for 2 weeks at doses of 10 to 160 micrograms/kg/d to normal animals to assess dose-response and toxicity. Subsequently, 40, 80, ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-07-15 00:00:00
abstract::Tumor necrosis factor-alpha (TNF-alpha), a cytokine possessing pleiotropic biological activities, is produced by leukemic lymphocytes in patients with chronic lymphocytic leukemia (CLL) and acts as an autocrine and paracrine growth factor in this disease. In this study, TNF-alpha levels were determined in 150 patients...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2002-08-15 00:00:00
abstract::Dentin matrix protein 1 (DMP1) is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family, a group of proteins initially described as mineralized extracellular matrices components. More recently, SIBLINGs have been implicated in several key steps of cancer progression, including angiogenes...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-08-298810
更新日期:2011-02-24 00:00:00