Abstract:
:Red blood cells deliver O(2) from the lungs to every cell in the human body. Reduced tissue oxygenation triggers increased production of erythropoietin by hypoxia-inducible factor 1 (HIF-1), which is a transcriptional activator composed of an O(2)-regulated alpha subunit and a constitutively expressed beta subunit. Hydroxylation of HIF-1alpha or HIF-2alpha by the asparaginyl hydroxylase FIH-1 blocks coactivator binding and transactivation. Hydroxylation of HIF-1alpha or HIF-2alpha by the prolyl hydroxylase PHD2 is required for binding of the von Hippel-Lindau protein (VHL), leading to ubiquitination and proteasomal degradation. Mutations in the genes encoding VHL, PHD2, and HIF-2alpha have been identified in patients with familial erythrocytosis. Patients with Chuvash polycythemia, who are homozygous for a missense mutation in the VHL gene, have multisystem pathology attributable to dysregulated oxygen homeostasis. Intense efforts are under way to identify small molecule hydroxylase inhibitors that can be administered chronically to selectively induce erythropoiesis without undesirable side effects.
journal_name
Bloodjournal_title
Bloodauthors
Semenza GLdoi
10.1182/blood-2009-05-189985subject
Has Abstractpub_date
2009-09-03 00:00:00pages
2015-9issue
10eissn
0006-4971issn
1528-0020pii
blood-2009-05-189985journal_volume
114pub_type
杂志文章,评审相关文献
BLOOD文献大全abstract::In children with acute lymphoblastic leukemia (ALL), the level of minimal residual disease (MRD) at the end of induction strongly predicts outcome, presumably because it measures both drug sensitivity and the number of leukemic cells requiring elimination. Children with high levels (> 10(-3) leukemic cells per marrow ...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:1996-06-15 00:00:00
abstract::The model of erythroleukemia caused by Spi-1/PU.1 transgenesis in mice is a multistage disease. A preleukemic step is characterized by an acute proliferation of proerythroblasts due to the arrest of differentiation provoked by Spi-1/PU.1. Later on, a blastic crisis occurs associated with somatic oncogenic mutations in...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-09-110510
更新日期:2008-03-15 00:00:00
abstract::Mice deficient for the transcription factor, interferon consensus sequence binding protein (ICSBP), are immunodeficient and develop disease symptoms similar to human chronic myeloid leukemia (CML). To elucidate the hematopoietic disorder of ICSBP(-/-) mice, we investigated the growth, differentiation, and leukemogenic...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-12-01 00:00:00
abstract::Defective function of dendritic cells (DC) in cancer has been recently described and may represent one of the mechanisms of tumor evasion from immune system control. We have previously shown in vitro that vascular endothelial growth factor (VEGF), produced by almost all tumors, is one of the tumor-derived factors resp...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-12-01 00:00:00
abstract::We have recently shown that proteasome inhibitor PS-341 induces apoptosis in drug-resistant multiple myeloma (MM) cells, inhibits binding of MM cells in the bone marrow microenvironment, and inhibits cytokines mediating MM cell growth, survival, drug resistance, and migration in vitro. PS-341 also inhibits human MM ce...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-08-2543
更新日期:2003-02-15 00:00:00
abstract::The mechanisms by which hematopoietic progenitor cells become lineage-committed remain poorly understood. A cloned subline of the AML14 cell line (AML14.3D10) that spontaneously differentiates to eosinophilic myelocytes in the absence of cytokine stimulation was obtained by limiting dilution. This subline exhibits aug...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-11-15 00:00:00
abstract::Secondary acute myeloid leukemias (AMLs) evolving from an antecedent myeloproliferative neoplasm (MPN) are characterized by a unique set of cytogenetic and molecular features distinct from de novo AML. Given the high frequency of poor-risk cytogenetic and molecular features, malignant clones are frequently insensitive...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2019000943
更新日期:2020-07-02 00:00:00
abstract::The signals that mediate T-cell infiltration during T-cell autoimmune diseases are poorly understood. The chemokine CCL21 (originally isolated by us and others as Exodus-2/6Ckine/SLC/TCA4) is highly potent and highly specific for stimulating T-cell migration. However, it is thought to be expressed only in secondary ly...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-05-1586
更新日期:2003-02-01 00:00:00
abstract::The effect of both congenital and acquired factor VII deficiency on the cuticle bleeding time (CBT) was evaluated in dogs. The CBT has been previously documented to be a sensitive indicator of factor VIII:C deficiency in hemophilic dogs. Serial CBT determinations were made on normal dogs treated with high-dose warfari...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1985-05-01 00:00:00
abstract::Prevention of erythrocyte dehydration is a potential therapeutic strategy for sickle cell disease. Increasing erythrocyte magnesium (Mg) could inhibit sickle cell dehydration by increasing chloride (CI) and water content and by inhibiting potassium chloride (K-CI) cotransport. In transgenic SAD 1 and (control) C57BL/6...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract::Human K562 erythroleukemia cells were transfected with human band 3 (anion exchanger 1 [AE1]) cDNA, using the pBabe retroviral vector. Stable K562 clones expressing band 3 were isolated by flow cytometry, and surface expression was quantified by immunoblotting. The function of band 3 expressed at the cell surface was ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-12-01 00:00:00
abstract::Chronic myelogenous leukemia (CML) is a malignant disease of the hematopoietic stem cell characterized by abnormal circulation and proliferation of malignant progenitors. In contrast to their normal counterparts, CML progenitors adhere poorly to bone marrow stroma or fibronectin (FN). Aside from anchoring progenitors ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-03-15 00:00:00
abstract::Characterization of hematopoietic cells and measurement of their proliferative potential is critical in many research and clinical applications. Because in vivo assay of human cells is not possible and xenogeneic assays are not yet routine, in vitro assays such as the long-term culture-initiating cell (LTC-IC) assay h...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-06-01 00:00:00
abstract::E-proteins are widely expressed basic helix-loop-helix (HLH) transcription factors that regulate differentiation in many cell lineages, including lymphoid, muscle, and neuronal cells. E-protein function is controlled by HLH inhibitors such as Id and SCL/TAL1 proteins, which recently have been suggested to play a role ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-01-069914
更新日期:2007-10-01 00:00:00
abstract::The granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) is a potential target for toxin-directed therapy, because it is overexpressed on many leukemias and solid tumors and apparently not on stem cells. To investigate the potential therapeutic use of GM-CSF toxins, we fused human GM-CSF to truncated fo...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-07-01 00:00:00
abstract::The mevalonate pathway produces many critical substances in cells, including sterols essential for membrane structure and isoprenoids vital to the function of many membrane proteins. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is a rate-limiting enzyme in the mevalonate pathway. Because cholesterol is a ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-07-2283
更新日期:2003-05-01 00:00:00
abstract::To determine whether a prior history of hepatosplenic candidiasis resulted in increased Candida-associated morbidity and mortality after marrow transplant, 15 consecutive patients with biopsy-proven hepatosplenic candidiasis were observed prospectively. All patients received amphotericin B before transplant. Amphoteri...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-10-15 00:00:00
abstract::An imbalance between cellular apoptosis and survival may be critical for the pathogenesis of lymphoma. Therefore, the gene expression pattern in lymph node preparations from patients with mantle cell lymphoma (MCL) was compared to the pattern in nonmalignant hyperplastic lymph nodes (HLs). Oligonucleotide microarray a...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v98.3.787
更新日期:2001-08-01 00:00:00
abstract::The SRC family kinases (SFKs) and the receptor tyrosine kinase c-Kit are activated in human acute myeloid leukemia (AML) cells. We show here that the SFKs LYN, HCK, or FGR are overexpressed and activated in AML progenitor cells. Treatment with the SFK and c-KIT inhibitor dasatinib selectively inhibits human AML stem/p...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-11-466425
更新日期:2013-09-12 00:00:00
abstract::The periprocedural management of patients receiving long-term oral anticoagulant therapy remains a common but difficult clinical problem, with a lack of high-quality evidence to inform best practices. It is a patient's thromboembolic risk that drives the need for an aggressive periprocedural strategy, including the us...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2012-06-415943
更新日期:2012-10-11 00:00:00
abstract::In most cases, the lack of Rh in Rh(null) red cells is associated with RHAG gene mutations. We explored the role of RhAG in the surface expression of Rh. Nonerythroid HEK293 cells, which lack Rh and RhAG, or erythroid K562 cells, which endogenously express RhAG but not Rh, were transfected with RhD and/or RhAG cDNAs u...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2002-08-01 00:00:00
abstract::The CC chemokine receptor 8 (CCR8) is expressed on monocytes and type 2 T lymphocytes. CCR8 is the sole receptor for the human CC chemokine I-309, as well as for viral monocyte inflammatory protein-I (vMIP-I), a human chemokine homologue induced in human cells by the Kaposi sarcoma-related human herpesvirus-8. Recentl...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v97.1.39
更新日期:2001-01-01 00:00:00
abstract::Human invariant natural killer T (iNKT) cells are a rare innate-like lymphocyte population that recognizes glycolipids presented on CD1d. Studies in mice have shown that these cells are heterogeneous and are capable of enacting diverse functions, and the composition of iNKT cell subsets can alter disease outcomes. In ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2019001903
更新日期:2020-03-12 00:00:00
abstract::Expression of the arterial marker molecule ephrinB2 in endothelial cells is a prerequisite for adequate remodeling processes of the developing or angiogenic vasculature. Although its role in these processes has been extensively studied, the impact of ephrinB2 on the remodeling of adult arteries is largely unknown. To ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-12-128835
更新日期:2008-07-01 00:00:00
abstract::The congenital sideroblastic anemias (CSAs) are relatively uncommon diseases characterized by defects in mitochondrial heme synthesis, iron-sulfur (Fe-S) cluster biogenesis, or protein synthesis. Here we demonstrate that mutations in HSPA9, a mitochondrial HSP70 homolog located in the chromosome 5q deletion syndrome 5...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-09-659854
更新日期:2015-12-17 00:00:00
abstract::T-cell prolymphocytic leukemia (T-PLL), a rare form of mature T-cell leukemias, and ataxia telangiectasia clonal proliferation, a related condition occurring in patients suffering from ataxia telangiectasia, have been associated to translocations involving the 14q32.1 or Xq28 regions, where are located the TCL1 and MT...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-03-01 00:00:00
abstract::Fas (CD95/Apo-1) mutations were previously reported as the genetic defect responsible for human lymphoproliferative syndrome associated with autoimmune manifestations (also known as autoimmune lymphoproliferative syndrome or Canale-Smith syndrome). We have identified 14 new heterozygous Fas mutations. Analysis of pati...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-10-15 00:00:00
abstract::The reported outcome of hematopoietic stem cell transplantation (HSCT) from HLA-mismatched family members has been inconsistent. The object of this study was to evaluate the true impact of HLA-mismatch by using recent data from a homogenous population, excluding HSCT procedures that used graft manipulations, and by co...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-02-0430
更新日期:2003-08-15 00:00:00
abstract::Three new human myeloma cell lines (U-1957, U-1958, and U-1996) have been established in vitro. The cell lines are Epstein-Barr virus (EBV) negative, monoclonal, and aneuploid and should thus represent malignant cell populations and not EBV-carrying non-neoplastic B lymphoblastoid cell lines. The myeloma origin of the...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-06-01 00:00:00
abstract::The pathophysiology of iron-induced compromised fertility in women with thalassemia major (TM) was evaluated in 26 adult TM females. Low gonadotropin secretion resulted in reduced ovarian antral follicle count and ovarian volume, but levels of anti-müllerian hormone (AMH), a sensitive marker for ovarian reserve indepe...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-06-360271
更新日期:2011-09-08 00:00:00