Abstract：
:Isocitrate dehydrogenase 1 mutation (IDH1-R132H) was recently identified in acute myeloid leukemia with normal cytogenetics. The mutant enzyme is thought to convert α-ketoglutarate to the pathogenic 2-hydroxyglutarate (2-HG) that affects DNA methylation via inhibition of ten-eleven translocation 2. However, the role of wild-type IDH1 in normal hematopoiesis and its relevance to acute myeloid leukemia is unknown. Here we showed that zebrafish idh1 (zidh1) knockdown by morpholino and targeted mutagenesis by transcription activator-like effector nuclease might induce blockade in myeloid differentiation, as evident by an increase in pu.1 and decrease in mpo, l-plastin, and mpeg1 expression, and significantly reduce definitive hematopoiesis. Morpholino knockdown of zidh2 also induced a blockade in myeloid differentiation but definitive hematopoiesis was not affected. The hematopoietic phenotype of zidh1 knockdown was not rescuable by zidh2 messenger RNA, suggesting nonredundant functions. Overexpression of human IDH1-R132H or its zebrafish ortholog resulted in 2-HG elevation and expansion of myelopoiesis in zebrafish embryos. A human IDH1-R132H-specific inhibitor (AGI-5198) significantly ameliorated both hematopoietic and 2-HG responses in human but not zebrafish IDH1 mutant expression. The results provided important insights to the role of zidh1 in myelopoiesis and definitive hematopoiesis and of IDH1-R132H in leukemogenesis.
journal_name
Bloodjournal_title
Bloodauthors
Shi X,He BL,Ma AC,Guo Y,Chi Y,Man CH,Zhang W,Zhang Y,Wen Z,Cheng T,Leung AYdoi
10.1182/blood-2014-09-601187subject
Has Abstractpub_date
2015-05-07 00:00:00pages
2974-84issue
19eissn
0006-4971issn
1528-0020pii
blood-2014-09-601187journal_volume
125pub_type
杂志文章相关文献
BLOOD文献大全abstract：:The replating capability of human umbilical cord blood (CB) multipotential (CFU-GEMM) progenitors was assessed in vitro as an estimate of self-renewal using erythropoietin (Epo), steel factor (SLF), and either fetal bovine serum (FBS) or CB plasma. This study found a much higher replating efficiency for CB CFU-GEMM th...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1993-02-15 00:00:00
abstract：:Until recently, IgE-activated mast cells have been regarded merely as effector cells of adaptive immune responses, involved in allergic reactions and mucosal immunity to parasites. Herein, we report that murine dermal mast cells, activated by local administration of a cream containing the synthetic TLR7 ligand imiquim...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2006-07-036889
更新日期：2007-08-01 00:00:00
abstract：:The effect of cyclosporine A (CyA) on the ability of the human immunodeficiency virus type 1 (HIV-1) to infect the H-9 T-cell leukemic line, as well as interleukin-2 (IL-2)-grown human peripheral blood-derived lymphocytes, has been studied. Pretreatment of H-9 cells and human lymphocytes with CyA over 24 hours complet...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1988-12-01 00:00:00
abstract：:Folylpoly-gamma-gluatamate synthetase (FPGS) catalyzes the polyglutamylation and thus intracellular retention of folates and antifolates (eg, methotrexate; MTX) through the addition of multiple glutamate equivalents to their gamma-carboxyl residue. Since polyglutamylation of antifolates is crucial for their pharmacolo...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2008-08-173799
更新日期：2009-04-30 00:00:00
abstract：:The RUNX1/AML1 gene is the most frequently mutated gene in human leukemia. Conditional deletion of Runx1 in adult mice results in an increase of hematopoietic stem cells (HSCs), which serve as target cells for leukemia; however, Runx1(-/-) mice do not develop spontaneous leukemia. Here we show that maintenance of Runx...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2009-07-232249
更新日期：2010-02-25 00:00:00
abstract：:Activated protein C is a potent anticoagulant and profibrinolytic enzyme that can be derived from the vitamin-K-dependent serine protease zymogen, protein C, by the action of thrombin. Protein C antigen concentration was determined in plasmas from normals (n = 40) and from 38 patients with intravascular coagulation as...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1982-07-01 00:00:00
abstract：:Normal human B cell proliferation is controlled by various immunoregulatory signals including the T cell-derived lymphokine B cell growth factor (BCGF). The role of BCGF in the regulation of malignant B cell proliferation is unclear. Therefore, we studied the proliferative response of purified chronic lymphocytic leuk...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1986-04-01 00:00:00
abstract：:Fetal hemoglobin (Hb F) production in sickle cell (SS) disease and in normal individuals varies over a 20-fold range and is under genetic control. Previous studies suggested that variant Hb F levels might be controlled by genetic loci separate from the beta-globin complex on chromosome 11. Using microscopic radial imm...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1992-08-01 00:00:00
abstract：:Epstein-Barr virus (EBV) is a ubiquitous virus that establishes a latent infection within the host and in some cases can lead to the development of EBV-associated lymphomas, lymphoproliferative disorders, hemophagocytic lymphohistiocytosis, solid tumors, and other diseases. We studied the clinical significance of dete...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2015-09-672030
更新日期：2016-04-21 00:00:00
abstract：:The calcium, sodium, and magnesium permeability of erythrocytes from blood stored at 4 degrees C in various anticoagulant media has been studied and compared to that of fresh erythrocytes. Passive influx of CA2+ was measured at 37 degrees C in cells pretreated to abolish Ca2+ pumping and was up to fivefold greater for...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1982-07-01 00:00:00
abstract：:Twenty-four adults with ALL were treated with AMSA alone or in combination. Twenty-two were treated at time of relapse and two patients after failing primary induction therapy. All had been treated with anthracyclines prior to receiving AMSA. Of the 22 patients with ALL in relapse, 4 achieved a complete remission. Two...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1982-11-01 00:00:00
abstract：:The role of fibroblast growth factors (FGFs) in blood vessel formation has remained unclear. We used differentiating stem-cell cultures (embryoid bodies) and teratomas to show that FGF receptor-1 (FGFR-1) exerts a negative regulatory effect on endothelial cell function in these models. Embryoid bodies lacking expressi...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2007-01-067314
更新日期：2007-12-15 00:00:00
abstract：:Gene therapy for hemophilia A requires efficient delivery of the factor VIII gene and sustained protein expression at circulating levels of at least 1% to 2% of normal. Adeno-associated viral type 2 (AAV2) vectors have a number of advantages over other viral vectors, including an excellent safety profile and persisten...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2003-01-0292
更新日期：2003-09-15 00:00:00
abstract：:Acute myeloid leukemia (AML) may follow a JAK2-positive myeloproliferative neoplasm (MPN), although the mechanisms of disease evolution, often involving loss of mutant JAK2, remain obscure. We studied 16 patients with JAK2-mutant (7 of 16) or JAK2 wild-type (9 of 16) AML after a JAK2-mutant MPN. Primary myelofibrosis ...
journal_title：Blood
pub_type： 杂志文章,多中心研究
doi：10.1182/blood-2009-08-236596
更新日期：2010-04-08 00:00:00
abstract：:The regulation of plasmin generation on cell surfaces is of critical importance in the control of vascular homeostasis. Cell-derived microparticles participate in the dissemination of biological activities. However, their capacity to promote plasmin generation has not been documented. In this study, we show that endot...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2007-02-069997
更新日期：2007-10-01 00:00:00
abstract：:We have investigated whether recombinant erythropoietin (r-Epo) elicits a change in intracellular free calcium (IFC) in purified Epo-responsive cells in spleens of mice treated with phenylhydrazine. Colony-forming units (CFU-E) were prepared by negative selection through immunologic panning. Anti-Forssman, Mac-1, Ia, ...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1989-05-01 00:00:00
abstract：:Surface marker and gene rearrangement data have supported various hypotheses about the origin of the malignant cell in Hodgkin's disease. Cytogenetic data about this disorder, however, are very scanty. To determine if any chromosomal abnormalities that could add further information to this controversial point are pres...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1988-06-01 00:00:00
abstract：:Targeted sequencing of 103 leukemia-associated genes in leukemia cells from 841 treatment-naive patients with chronic lymphocytic leukemia (CLL) identified 89 (11%) patients as having CLL cells with mutations in genes encoding proteins that putatively are involved in hedgehog (Hh) signaling. Consistent with this findi...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2018-09-873695
更新日期：2019-06-20 00:00:00
abstract：:Hypoxia is a strong stimulus for the transcription of a set of genes, including erythropoietin and vascular endothelial growth factor. Here we report on the cloning, functional significance, and expression of a complementary DNA (cDNA) that is involved in hypoxia-mediated expression of these 2 genes. The full-length c...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：2000-07-15 00:00:00
abstract：:Considerable evidence indicates that activation of the contact system of intrinsic coagulation plays a role in the pathogenesis of septic shock. To monitor contact activation in patients with sepsis, we developed highly sensitive radioimmunoassays (RIAs) for factor XIIa-Cl(-)-inhibitor (Cl(-)-Inh) and kallikrein-Cl(-)...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1988-12-01 00:00:00
abstract：:Uncontrolled activation of the complement system against endothelial and blood cells is central to the pathogenesis of atypical hemolytic uremic syndrome (aHUS). aHUS patients frequently carry mutations in the inhibitory complement regulator factor H (FH). Mutations cluster in domains 19 and 20 (FH19-20), which are cr...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2015-11-680009
更新日期：2016-06-02 00:00:00
abstract：:Large granular lymphocyte (LGL) leukemia results from clonal expansion of CD3+ cytotoxic T lymphocytes or CD3- natural killer (NK) cells. Chronic antigen stimulation is postulated to promote long-term survival of LGL leukemia cells through constitutive activation of multiple survival pathways, resulting in global dysr...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2017-09-808816
更新日期：2018-06-21 00:00:00
abstract：:The endothelium, as the interface between blood and all tissues, plays a critical role in inflammation. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid, highly abundant in plasma, that potently regulates endothelial responses through interaction with its receptors (S1PRs). Here, we studied the role of S1PR2 ...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2012-11-467191
更新日期：2013-07-18 00:00:00
abstract：:Protein disulfide isomerase (PDI) derived from intravascular cells is required for thrombus formation. However, it remains unclear whether platelet PDI contributes to the process. Using platelet-specific PDI-deficient mice, we demonstrate that PDI-null platelets have defects in aggregation and adenosine triphosphate s...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2013-03-492504
更新日期：2013-08-08 00:00:00
abstract：:Natural killer (NK) cells can alter the outcome of hematopoietic cell transplantation (HCT) if donor alloreactivity targets the recipient. Since most NK cells express inhibitory killer-immunoglobulin receptors (KIRs), we hypothesized that the susceptibility of recipient cells to donor NK cell-mediated lysis is genetic...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2007-01-065383
更新日期：2007-06-01 00:00:00
abstract：:About 50% of the Philadelphia-positive acute leukemias undergo molecular rearrangements outside the now classical bcr sequence (or M-BCR-1) rearranged in chronic myeloid leukemia (CML). Most of the breakpoints on chromosome 22 have been shown to be clustered in a 10.8-kb region of the first intron of the BCR gene (cal...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1989-04-01 00:00:00
abstract：:An unusual group of human B-cell tumors with cellular features of chronic lymphocytic leukemia or lymphoplasmacytoid leukemia, together with high levels of a monoclonal IgG serum protein, has been investigated. Analysis of tumor-derived VH genes of neoplastic B lymphocytes was used to determine the clonal relationship...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1998-01-01 00:00:00
abstract：:The t(8;21) RUNX1-ETO translocation is one of the most frequent cytogenetic abnormalities in acute myeloid leukemia (AML). In RUNX1-ETO(+) patient samples, differing classes of activating c-KIT receptor tyrosine kinase mutations have been observed. The most common (12%-48%) involves mutations, such as D816V, which occ...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2011-02-338228
更新日期：2012-02-09 00:00:00
abstract：:Ruxolitinib is JAK1/JAK2 inhibitor with established clinical benefit in myelofibrosis (MF). We analyzed long-term outcomes of 107 patients with intermediate-2 or high-risk MF receiving ruxolitinib at MD Anderson Cancer Center (MDACC) on phase 1/2 trial. After a median of 32 months of follow-up, 58 patients (54%) were ...
journal_title：Blood
pub_type： 杂志文章,多中心研究
doi：10.1182/blood-2012-02-414631
更新日期：2012-08-09 00:00:00
abstract：:Purified human high-mol-wt kininogen (HMWK), the cofactor of the contact phase of blood coagulation, migrated as a single band (approximately 110,000 mol wt) in a continuous buffer sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), but appeared as two separated bands (approximately 120,000 and 105,0...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1986-08-01 00:00:00
