Abstract:
:Bruton's tyrosine kinase (BTK) was previously demonstrated to be a mediator of oxidative stress-induced apoptosis in irradiated neoplastic B-cells and B-cell precursors. Defective BTK expression in leukaemic B-cell precursors from infants with t(4;11) acute lymphoblastic leukaemia has been associated with radiation resistance. The present study examined whether BTK mediates apoptosis during oxidative stress by interfering with the anti-apoptotic function of signal transducer and activator of transcription 3 (STAT3). BTK physically associated with and tyrosine phosphorylated STAT3; this association was promoted by pervanadate (PV)-induced oxidative stress. The BTK/STAT3 interaction appeared to prevent STAT3 response to oxidative stress, because PV-induced STAT3 activation was markedly enhanced in DT40 chicken lymphoma B-cells that were rendered BTK-deficient by targeted disruption of the btk gene as well as in BTK-deficient RAMOS-1 human lymphoma B-cells. These BTK-deficient cells were highly resistant to oxidative stress-induced apoptosis triggered by PV treatment. Reconstitution of BTK-deficient DT40 cells with wild-type human BTK gene eliminated the amplification of the STAT3 response and restored the PV-induced apoptotic signal. Similarly, while the BTK-positive NALM-6 human leukaemic B-cell precursor cell line showed no STAT3 activation after PV treatment and was exquisitely sensitive to PV-induced apoptosis, PV failed to induce apoptosis in BTK-deficient RAMOS-1 human lymphoma B-cells that showed a robust STAT3 response. These results provide unprecedented biochemical and genetic evidence for a unique mode of cross-talk that occurs between BTK and STAT3 pathways during oxidative stress, whereby BTK may trigger apoptosis via negative regulation of the anti-apoptotic STAT3 activity.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Uckun F,Ozer Z,Vassilev Adoi
10.1111/j.1365-2141.2006.06468.xsubject
Has Abstractpub_date
2007-02-01 00:00:00pages
574-89issue
4eissn
0007-1048issn
1365-2141pii
BJH6468journal_volume
136pub_type
杂志文章abstract::Haemophilia A is an attractive target for gene therapy. We designed a haemophilia A gene therapy strategy involving the genetic modification of haematopoietic stem cells to achieve tissue-specific expression of a factor VIII (FVIII) transgene in the megakaryocytic lineage. Platelets would then serve as vehicles to sto...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2004.05244.x
更新日期:2004-12-01 00:00:00
abstract::In an ongoing effort to identify point mutations causing beta-thalassaemia, we have found two previously unreported mutations which are located in the Poly A site of the beta-globin gene. The screening programme used amplified DNA and dot-blot hybridization with several 32P-labelled oligonucleotide probes. DNA samples...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1990.tb02627.x
更新日期:1990-05-01 00:00:00
abstract::Platelets have recently been shown to trigger intrinsic coagulation by two alternative pathways, protect active clotting factors from inactivation by plasma inhibitors and catalyse intrinsic coagulation reactions on the platelet surface to form fibrin. To determine whether these platelet coagulant activities (PCA) mig...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2141.1976.tb00946.x
更新日期:1976-03-01 00:00:00
abstract::A new method of in vivo bioassay for erythropoietin (EPO) is described. This method is based on the measurement of immature reticulocytes in EPO-treated mice using an automatic microcell counter, and is simpler and more precise than the existing methods of polycythaemic mouse assay and starved rat assay. Normal mice w...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1991.tb08595.x
更新日期:1991-03-01 00:00:00
abstract::Primary mediastinal B-cell lymphoma (PMBL) shows chromosome 9p anomalies in 50% of cases. Based on reports that p16INK4A gene, located on this chromosomal arm, is frequently altered in aggressive lymphomas, we analysed for alterations of this gene in 27 cases of PMBL, which were part of a series of 32 PMBL cases that ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1999.01678.x
更新日期:1999-10-01 00:00:00
abstract::In HbSC disease, as in sickle cell anaemia, there is a spectrum of clinical severity. A reduced mean corpuscular volume and haemoglobin concentration, traits typical of thalassaemia, might retard sickling. We therefore ascertained the prevalence of alpha-thalassaemia in 53 adults with HbSC disease and related alpha-gl...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1983.tb02164.x
更新日期:1983-11-01 00:00:00
abstract::Hepatitis E virus (HEV) is increasingly found to cause hepatitis in allogeneic haematopoietic stem cell transplantation (HSCT) patients. However, little is known about HEV infection in patients receiving haploidentical HSCT (haplo-HSCT). Here, we retrospectively evaluate the incidence and clinical course of HEV infect...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/bjh.15672
更新日期:2019-03-01 00:00:00
abstract::Three patients with an acute myeloid leukaemia (AML) showed a deletion of the short arm of chromosome 7 with loss of the deleted material. The 7p- anomaly originated from either a terminal or an interstitial deletion and it represented the only karyotypic aberration in all the three cases. According to the clinical, m...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1989.tb06267.x
更新日期:1989-01-01 00:00:00
abstract::The pattern of distribution of von Willebrand factor (VWF) in relatively large sheets of rat aortic endothelial cells (EC) obtained by the Häutchen technique were analysed by immunocytochemistry and light microscopy. EC were examined pre and post administration of a procoagulant mixture of factor Xa (F.Xa) and phospho...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1996.4661005.x
更新日期:1996-04-01 00:00:00
abstract::Fanconi anaemia (FA) is an autosomal recessive disease strongly predisposing to bone marrow failure and acute myeloid leukaemia (AML). Four FA genes, corresponding to complementation groups A, C, F and G, have been cloned, but the molecular functions of the corresponding proteins are unknown. The high risk of AML in F...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:
更新日期:2000-12-01 00:00:00
abstract::While imatinib and other tyrosine kinase inhibitors (TKIs) are highly efficacious in the treatment of chronic myeloid leukaemia (CML), some patients become refractory to these therapies. After confirming that interleukin-3 receptor (IL3R, CD123) is highly expressed on CD34(+) /CD38(-) BCR-ABL1(+) CML stem cells, we in...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.12978
更新日期:2014-09-01 00:00:00
abstract::Colony-stimulating factor-1 (CSF-1) is a specific haematopoietic growth factor that stimulates the production of macrophages by both bone marrow macrophage precursors (GM-CFC) and certain more mature peripheral tissue macrophages. The relationship of CSF-1 utilization and cell production by macrophage precursors at va...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1987.tb06157.x
更新日期:1987-12-01 00:00:00
abstract::The myelodysplastic syndromes (MDS) have a significant frequency of evolution into acute myeloid leukaemia (AML). Approximately 30% of MDS patients show activating mutations of the N-RAS proto-oncogene, and these patients are at increased risk of leukaemic evolution. Long-term survivors of aplastic anaemia (AA) and pa...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1995.tb05411.x
更新日期:1995-12-01 00:00:00
abstract::Two chemoattractants, the peptide N-formyl-met-leu-phe (FMLP), and the ether phospholipid, platelet activating factor (PAF), each stimulate a variety of in vitro responses in polymorphonuclear leucocytes (PMN). Because often more than one inflammatory mediator is active during inflammation, we determined the effect on...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1987.tb01302.x
更新日期:1987-06-01 00:00:00
abstract::The peripheral T-cell neoplasms are a biologically and clinically heterogeneous group of rare disorders that result from clonal proliferation of mature post-thymic lymphocytes. Natural killer (NK) cell neoplasms are included in this group. The World Health Organization classification of haemopoietic malignancies has d...
journal_title:British journal of haematology
pub_type: 杂志文章,实务指引,评审
doi:10.1111/j.1365-2141.2011.08651.x
更新日期:2011-05-01 00:00:00
abstract::Various levels of thrombin generation were induced by the infusion of a combination of factor Xa (F.Xa) and phosphatidylcholine/phosphatidylserine (PCPS) vesicles into normal dogs and non-human primates. In the dog, an immediate loss of von Willebrand factor antigen (vWF:Ag) with a progressive recovery to normal level...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1993.tb03219.x
更新日期:1993-12-01 00:00:00
abstract::Smoking causes atherosclerosis, and smokers have increased thromboxane (TXA2) formation. As aspirin inhibits TXA2 production we speculated that smokers would preferentially profit from inhibition of the TXA2 pathway by aspirin. Increased expression of P-selectin, a constituent of the alpha-granules of platelets, and i...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1365-2141.1998.00883.x
更新日期:1998-09-01 00:00:00
abstract::Standard treatment for classical Hodgkin lymphoma (cHL) is poorly tolerated in older patients and results disappointing. We assessed safety and efficacy of brentuximab vedotin (BV), in previously untreated patients with cHL unfit for standard treatment due to age, frailty or comorbidity. The primary outcome was comple...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.17073
更新日期:2020-09-14 00:00:00
abstract::Stage I/IIA follicular lymphoma (FL) is considered a localised disease that can be adequately treated with radiotherapy alone. Bone marrow (BM) and peripheral blood (PB) involvement in FL was investigated by polymerase chain reaction (PCR) in a series of 24 consecutive patients with histologically revised diagnosis an...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2007.06545.x
更新日期:2007-05-01 00:00:00
abstract::A mechanism has been proposed in which nitric oxide (NO) may bind to cysteine beta93 and be transported by haemoglobin from the lungs to the tissues and modify vascular tone. In addition, it has been reported that treatment of sickle cell anaemia blood with 80 p.p.m. NO gas in air shifts the oxygen affinity, as measur...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.02203.x
更新日期:2000-08-01 00:00:00
abstract::This report describes a case of chronic myelomonocytic leukaemia (CMML) in whom a complete remission was achieved and sustained 15 months after treatment with 25-OH vitamin D3. No side-effects were observed. Although vitamin D1 has been used in the treatment of myelodysplastic syndromes, to our knowledge this is the f...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1993.tb03230.x
更新日期:1993-12-01 00:00:00
abstract::To assess sources of variability in platelet function tests in normal subjects, 64 healthy young adults were tested on 2-6 occasions at 2 week intervals using four methods: platelet aggregation (AGG) in platelet-rich plasma (PRP) in the Bio/Data PAP-4 Aggregometer (BD) and Chrono-Log Lumi-Aggregometer (CL); and AGG in...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.12827
更新日期:2014-06-01 00:00:00
abstract::We studied erythrocyte calcium levels and uptake in a group of patients with sickle haemoglobinopathies of different clinical severity in an attempt to relate these measurements to the production of irreversibly sickled cells and disease severity. Erythrocyte calcium levels were measured by atomic absorption spectrosc...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1978.tb05829.x
更新日期:1978-12-01 00:00:00
abstract::Positive selected haematopoietic stem cells are increasingly used for allogeneic transplantation with the CD34 antigen employed in most separation techniques. However, the recently described pentaspan molecule CD133 appears to be a marker of more primitive haematopoietic progenitors. Here we report our experience with...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2003.04747.x
更新日期:2004-01-01 00:00:00
abstract::Children with Down syndrome (DS) have a greater risk for developing both acute lymphoblastic leukaemia (ALL) and significant adverse effects of chemotherapy. We investigated their outcome with, and tolerance of, treatment protocols for relapsed ALL optimized in the paediatric population without DS. Probability of surv...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.12348
更新日期:2013-07-01 00:00:00
abstract::Human bone marrow mesenchymal stem cells (MSC) generate, via a fibroblast colony-forming unit (CFU-F), osteo-chondroblastic cells as well as adipocytes and stromacytes. To date, these stem cells are isolated indirectly using a cell culture method and phenotyped as CD45 negative while the in vivo counterparts are undet...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2003.04469.x
更新日期:2003-08-01 00:00:00
abstract::Eighty-two patients with bleeding, disorders registered with our centre were screened for infection with hepatitis G virus (HGV). 80 patients were positive for hepatitis C (HCV) antibodies, 66 of whom (83%) were HCV PCR positive. 11 patients (13%) were HGV RNA-positive, a similar prevalence rate to that of other studi...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1997.4133220.x
更新日期:1997-11-01 00:00:00
abstract::Up-regulation of Fas/APO-1 (CD95) on haematopoietic progenitors and Fas-mediated apoptosis have been suggested to occur in a possible pathological mechanism in some bone marrow failure syndromes. We examined the expression of Fas antigen and susceptibility to Fas-mediated suppression of donor-derived haematopoietic ce...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.02022.x
更新日期:2000-05-01 00:00:00
abstract::Minor histocompatibility antigens (mHAs) are major histocompatibility complex (MHC)-associated peptides, which trigger T-cell responses that mediate graft versus host disease (GVHD) and graft versus leukaemia effects. We recently identified a new mHA epitope, termed ACC-1, which is presented by HLA-A*2402 and encoded ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2004.04823.x
更新日期:2004-03-01 00:00:00
abstract::Overt ischaemic stroke is one of the most devastating complications in children with sickle cell disease (SCD). The compensatory response to anaemia in SCD includes an increase in cerebral blood flow (CBF) by accessing cerebrovascular dilatory reserve. Exhaustion of dilatory reserve secondary to anaemic stress may lea...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.14424
更新日期:2017-01-01 00:00:00