Abstract:
:Recent studies have identified several populations of progenitor cells in the human thymus. The hematopoietic precursor activity of these populations has been determined. The most primitive human thymocytes express high levels of CD34 and lack CD1a. These cells acquire CD1a and differentiate into CD4(+)CD8(+) through CD3(-)CD4(+)CD8(-) and CD3(-)CD4(+) CD8alpha+beta- intermediate populations. The status of gene rearrangements in the various TCR loci, in particular of TCRdelta and TCRgamma, has not been analyzed in detail. In the present study we have determined the status of TCR gene rearrangements of early human postnatal thymocyte subpopulations by Southern blot analysis. Our results indicate that TCRdelta rearrangements initiate in CD34(+)CD1a- cells preceding those in the TCRgamma and TCRbeta loci that commence in CD34(+)CD1a+ cells. Furthermore, we have examined at which cellular stage TCRbeta selection occurs in humans. We analyzed expression of cytoplasmic TCRbeta and cell-surface CD3 on thymocytes that lack a mature TCRalphabeta. In addition, we overexpressed a constitutive-active mutant of p56(lckF505) by retrovirus-mediated gene transfer in sequential stages of T-cell development and analyzed the effect in a fetal thymic organ culture system. Evidence is presented that TCRbeta selection in humans is initiated at the transition of the CD3(-)CD4(+)CD8(-) into the CD4(+)CD8alpha+beta- stage.
journal_name
Bloodjournal_title
Bloodauthors
Blom B,Verschuren MC,Heemskerk MH,Bakker AQ,van Gastel-Mol EJ,Wolvers-Tettero IL,van Dongen JJ,Spits Hsubject
Has Abstractpub_date
1999-05-01 00:00:00pages
3033-43issue
9eissn
0006-4971issn
1528-0020journal_volume
93pub_type
杂志文章相关文献
BLOOD文献大全abstract::Germline mutations of the CDKN2A (p16(INK4A)) tumor suppressor gene predispose patients to melanoma and pancreatic carcinoma. In contrast, mutations of the murine CDKN2A gene predispose BALB/c mice to pristane-induced plasmacytoma. We describe here a family in which a germline mutation of CDKN2A is present in 4 indivi...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-03-01 00:00:00
abstract::Deregulation of Notch signaling has been linked to the development of T-cell leukemias and several solid malignancies. Yet, it is unknown whether Notch signaling is involved in the pathogenesis of mycosis fungoides and Sézary syndrome, the most common subtypes of cutaneous T-cell lymphoma. By immunohistochemistry of 4...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-12-260216
更新日期:2010-10-07 00:00:00
abstract::Long-term survival is now an expected outcome after hematopoietic cell transplantation (HCT). However, the burden of morbidity long-term after HCT remains unknown. We examined the magnitude of risk of chronic health conditions reported by 1022 HCT survivors and their siblings (n = 309). A severity score (grades 1 [mil...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-06-229369
更新日期:2010-10-28 00:00:00
abstract::Keratinocyte growth factor (KGF) is important in tissue repair and wound healing and its administration can abrogate chemical- and radiation-induced tissue damage in rodents. We investigated KGF as a therapeutic agent for the prevention of graft-versus-host disease (GVHD)-induced tissue damage, morbidity, and mortalit...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-11-15 00:00:00
abstract::The process of dendritic cell (DC) maturation, critical for effective DC-based immunotherapy, also alters the proteasome such that peptides presented in the context of HLA class I are generated not by the constitutive proteasome, but by the immunoproteasome. Cytotoxic T lymphocytes (CTLs) induced by such DCs might not...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-04-083188
更新日期:2007-12-15 00:00:00
abstract::Wilms' tumor 1 (WT1) is constantly expressed in leukemic cells of acute leukemia and myelodysplastic syndrome (MDS). A T-cell receptor (TCR) that specifically reacts with WT1 peptide in the context of HLA-A*24:02 has been identified. We conducted a first-in-human trial of TCR-gene transduced T-cell (TCR-T-cell) transf...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2017-06-791202
更新日期:2017-11-02 00:00:00
abstract::Selinexor is the first oral selective inhibitor of nuclear export compound tested for cancer treatment. Selinexor has demonstrated a safety therapy profile with broad antitumor activity against solid and hematological malignancies in phases 2 and 3 clinical trials (#NCT03071276, #NCT02343042, #NCT02227251, #NCT0311056...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2016-11-752840
更新日期:2017-08-31 00:00:00
abstract::The importance of the second messengers calcium (Ca(2+)) and diacylglycerol (DAG) in platelet signal transduction was established more than 30 years ago. Whereas protein kinase C (PKC) family members were discovered as the targets of DAG, little is known about the molecular identity of the main Ca(2+) sensor(s). We he...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-04-218768
更新日期:2009-09-17 00:00:00
abstract::Human cord blood (CB) offers an attractive source of cells for clinical transplants because of its rich content of cells with sustained repopulating ability in spite of an apparent deficiency of cells with rapid reconstituting ability. Nevertheless, the clonal dynamics of nonlimiting CB transplants remain poorly under...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-06-508432
更新日期:2013-10-31 00:00:00
abstract::The transcription factor runt-related transcription factor 1 (Runx1) is essential for the establishment of definitive hematopoiesis during embryonic development. In adult blood homeostasis, Runx1 plays a pivotal role in the maturation of lymphocytes and megakaryocytes. Furthermore, Runx1 is required for the regulation...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-09-382390
更新日期:2012-05-03 00:00:00
abstract::Drug-induced immune thrombocytopenia (DITP) is an adverse drug effect mediated by drug-dependent antibodies. Intravenous immunoglobulin (IVIG) is frequently used to treat DITP and primary immune thrombocytopenia (ITP). Despite IVIG's proven beneficial effects in ITP, its efficacy in DITP is unclear. We have establishe...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-02-268326
更新日期:2010-09-16 00:00:00
abstract::Megakaryoblastic leukemia 1 (MKL1), identified as part of the t(1;22) translocation specific to acute megakaryoblastic leukemia, is highly expressed in differentiated muscle cells and promotes muscle differentiation by activating serum response factor (SRF). Here we show that Mkl1 expression is up-regulated during mur...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-09-180596
更新日期:2009-03-19 00:00:00
abstract::Cytokine expression was analyzed in CD14++ regular monocytes and in the novel subset of CD14+/CD16+ small monocytes. Biologic activity for tumor necrosis factor (TNF), interleukin-1 (IL-1), and IL-6 in the supernatant of elutriator-enriched, cell sorter-purified small monocytes was about 10-fold lower compared with re...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-01-15 00:00:00
abstract::CD8alpha+ dendritic cells (DCs) represent a functionally distinct DC subset in vivo, which plays a critical role in initiating various cellular immune responses. However, the committed precursor of CD8alpha+ DCs remains to be identified. We reported here that murine splenic CD8alpha+CD11c- lineage phenotype (Lin)- cel...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v100.2.569
更新日期:2002-07-15 00:00:00
abstract::Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative disorders characterized by an increased incidence of thrombo-hemorrhagic complications. The acquired somatic Janus kinase 2 (JAK2) V617F mutation is present in the majority of PV and ET patients. Because aberrant protein Tyr-phosp...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-12-196535
更新日期:2010-01-21 00:00:00
abstract::This study includes 47 normal subjects and 25 hemophilia B patients without inhibitor(s), showing different factor IX coagulant activity and antigen levels. Genomic DNA, digested with various restriction endonucleases, was hybridized with two different factor IX probes, ie, the cDNA and the subgenomic probe for the in...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::The introduction of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib has dramatically changed the management of chronic lymphocytic leukemia (CLL). Although responses have been durable in the majority of patients, relapses do occur, especially in the high-risk patient population. Most relapses occur as the result ...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2016-09-693598
更新日期:2017-03-09 00:00:00
abstract::Both SDF-1 and CXCR4 disruption are lethal to mice at the embryonic stage and cause abnormalities in B lymphopoiesis, myelopoiesis, cardiogenesis, vasculogenesis, and cerebellar development. To investigate the role of SDF-1 and CXCR4 in hematopoiesis during the adult stage, mice reconstituted with bone marrow-derived ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-09-15 00:00:00
abstract::Twenty-six patients with progressive Hodgkin's disease after conventional chemotherapy received intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT); 19 also received additional involved-field radiotherapy. Twenty-one patients [81%, 95% confidence intervals (CI) 61% to 94%] attained complete (...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-06-01 00:00:00
abstract::Host defenses in the human neonate are limited by immaturity in phagocytic immunity. Such limitations seem to predispose infected newborns to neutropenia from an exhaustion of the neutrophil reserve. Among the critical defects thus far identified in neonatal phagocytic immunity is a specific reduction in the capacity ...
journal_title:Blood
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1994-09-01 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::Direct sequencing of VWF genomic DNA in 21 patients with type 3 von Willebrand disease (VWD) failed to reveal a causative homozygous or compound heterozygous VWF genotype in 5 cases. Subsequent analysis of VWF mRNA led to the discovery of a deletion (c.221-977_532 + 7059del [p.Asp75_Gly178del]) of VWF in 7 of 12 white...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-08-173278
更新日期:2009-07-30 00:00:00
abstract::The diagnosis of heparin-induced thrombocytopenia (HIT) requires detection of antibodies to the heparin/platelet factor 4 (PF4) complexes via enzyme-linked immunosorbent assay. Addition of excess heparin to the sample decreases the optical density by 50% or more and confirms the presence of these antibodies. One hundr...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-01-262659
更新日期:2010-09-09 00:00:00
abstract::To understand the regulatory mechanism of erythropoietin (EPO) receptor (EPOR) gene expression, the effect of EPO on the steady-state level of EPOR mRNA was examined using the human EPO-dependent cell line UT-7 as a model system. We found that the treatment of UT-7 cells with EPO resulted in a transient decrease of th...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-02-15 00:00:00
abstract::Recent studies suggest that the evolutionary history of a cancer is important in forecasting clinical outlook. To gain insight into the clonal dynamics of multiple myeloma (MM) and its possible influence on patient outcomes, we analyzed whole exome sequencing tumor data for 333 patients from Myeloma XI, a UK phase 3 t...
journal_title:Blood
pub_type: 杂志文章,随机对照试验
doi:10.1182/blood-2016-11-750612
更新日期:2017-10-05 00:00:00
abstract::Stem cells of highly regenerative organs including blood are susceptible to endogenous DNA damage caused by both intrinsic and extrinsic stress. Response mechanisms to such stress equipped in hematopoietic stem cells (HSCs) are crucial in sustaining hematopoietic homeostasis but remain largely unknown. In this study, ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-01-330050
更新日期:2011-09-15 00:00:00
abstract::Perforin (Prf1) and granzyme B (GzmB) are essential effector molecules for natural killer (NK)-cell cytotoxicity, but how Prf1 and GzmB expression is regulated during arming of NK cells is poorly defined. We show that human microRNA (miR)-27a* is a negative regulator of NK-cell cytotoxicity by silencing Prf1 and GzmB ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-04-347526
更新日期:2011-11-17 00:00:00
abstract::Six hundred twelve eligible, previously untreated patients with active multiple myeloma and at least some data available for analysis were entered into a randomized trial (Southwest Oncology Group [SWOG] Phase III myeloma study 8229/30), in which the prognostic significance of pretreatment serum beta 2 microglobulin l...
journal_title:Blood
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1990-02-15 00:00:00
abstract::Previous studies of follicular lymphoma (FL) patients treated heterogeneously have suggested that decreased numbers of regulatory T cells correlates with improved survival. We studied advanced-stage FL patients from a single institution phase 2 trial. All patients were treated uniformly with multiagent chemotherapy an...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-07-235598
更新日期:2010-01-14 00:00:00
abstract::The treatment of mice with high doses of 5-fluorouracil (5-FU) results in an enrichment of primitive hematopoietic progenitors. Using this procedure, we obtained a new class of murine hematopoietic colonies that had very high secondary plating efficiencies in vitro and could differentiate into not only myeloid cells b...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-07-15 00:00:00