Abstract:
:In this study, quiescent bone marrow-derived CD34+ erythroid burst-forming units (BFU-E) were found to be resistant to the inhibitory effects of tumour necrosis factor (TNF)-alpha and -beta as well as interferon (IFN)-alpha, -beta and -gamma, in contrast to those stimulated by a combination of erytrhropoietin (Epo) plus kit ligand (KL). Unexpectedly, we found that TNF-alpha also inhibited the apoptosis of quiescent normal human CD34+ BFU-E cells. Accordingly, TNF-alpha added to CD34+ cells cultured for 2 d in serum-free medium protected clonogeneic BFU-E from undergoing serum deprivation-mediated apoptosis. Furthermore, the prosurvival effect of TNF-alpha in quiescent CD34+ cells was consistent with its ability to induce phosphorylation of mitogen-activated protein kinase (MAPK) p42/44. However, when added to CD34+ cells that were stimulated by Epo + KL, TNF-alpha induced apoptosis and inhibited proliferation of BFU-E. To explain this intriguing differential sensitivity between unstimulated CD34+ cells versus those stimulated by Epo + KL, we examined the expression of apoptosis-regulating genes (FLIP, BCL-2, BCL-XL, BAD and BAX) in these cells. Of all the genes tested, FLIP became rapidly downregulated in CD34+ cells 24 h after stimulation with Epo + KL, suggesting that it may protect quiescent CD34+ BFU-E progenitors residing in the bone marrow from the inhibitory effects of inflammatory cytokines. Thus, we hypothesize that cycling cells may become more sensitive to proapoptotic stimuli (e.g. chemotherapy, inhibitory cytokines) than quiescent ones because of the downregulation of protective FLIP.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Ratajczak J,Kucia M,Reca R,Zhang J,Machalinski B,Ratajczak MZdoi
10.1046/j.1365-2141.2003.04566.xsubject
Has Abstractpub_date
2003-10-01 00:00:00pages
160-9issue
1eissn
0007-1048issn
1365-2141pii
4566journal_volume
123pub_type
杂志文章abstract::We report two cases of acute myeloid leukaemia FAB classification M4Eo with high white cell counts at presentation, who developed acute respiratory failure with pulmonary infiltrates on chest radiograph soon after commencing conventional cytotoxic chemotherapy plus all-trans retinoic acid (ATRA). We suggest that in pa...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.02043.x
更新日期:2000-06-01 00:00:00
abstract::A case of immune neutropenia following unrelated stem cell transplantation for chronic myeloid leukaemia is described. The neutropenia developed following herpes zoster viral infection and was associated with antibodies to the human neutrophil antigen (HNA)-2a (formerly known as NB1). The neutropenia was prolonged, pr...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2001.02779.x
更新日期:2001-05-01 00:00:00
abstract::Deregulated Hedgehog (Hh) signalling activity may be associated with a broad range of cancer types and hence has become an attractive target for therapeutic intervention. Although initial haematological interest focused on the therapeutic targeting of this pathway in chronic myeloid leukaemia), small molecule inhibito...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/bjh.13426
更新日期:2015-08-01 00:00:00
abstract::Twenty-six members of four generations of one family in which a man was diagnosed in 1961 as having von Willebrand's disease (vWD) have been studied. Subtype IIB vWD and autosomal dominant inheritance was identified in 19 individuals with bleeding signs varying in severity and frequency. The absence of high molecular ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1988.tb02406.x
更新日期:1988-08-01 00:00:00
abstract::Increased haemoglobin (Hb) A2 levels associated with reduced mean corpuscular volume (MCV) and Hb content per cell (MCH) are the most typical features of heterozygous beta thalassaemia. However, double heterozygotes for alpha and beta thalassaemia may have normal MCV and MCH but Hb A2 always in the carrier range. In t...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1993.tb03042.x
更新日期:1993-05-01 00:00:00
abstract::Flow cytometry was used to determine the percentage and number of circulating CD34+ cells in fetal blood from 100 pregnancies at 13-38 weeks gestation. When expressed as a percentage of the total number of lymphocytes, the proportion of CD34+ cells decreased exponentially from a mean of 11.1% (9.2 x 10(7)/l) at 13 wee...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1994.tb08328.x
更新日期:1994-07-01 00:00:00
abstract::Diamond Blackfan anaemia (DBA) is a rare, genetically and clinically heterogeneous, inherited red cell aplasia. Classical DBA affects about seven per million live births and presents during the first year of life. However, as mutated genes have been discovered in DBA, non-classical cases with less distinct phenotypes ...
journal_title:British journal of haematology
pub_type: 共识发展会议,杂志文章
doi:10.1111/j.1365-2141.2008.07269.x
更新日期:2008-09-01 00:00:00
abstract::The integration of molecular and clinical information to tailor treatments remains an important research challenge in chronic lymphocytic leukaemia (CLL). This study aimed to identify genomic lesions associated with a poor outcome and a higher risk of histological transformation. A mono-institutional cohort of 147 cas...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2141.2011.08789.x
更新日期:2011-09-01 00:00:00
abstract::Relapse of childhood acute lymphoblastic leukaemia (ALL) involving the eye is a rare but challenging problem. Twenty cases occurred in patients treated on the Medical Research Council United Kingdom Acute Lymphoblastic Leukaemia XI and ALL97 trials between 1991 and 2001, representing 2.2% of ALL relapses. Seventeen oc...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1046/j.1365-2141.2003.04280.x
更新日期:2003-04-01 00:00:00
abstract::We report a case of persistent infection with human parvovirus B19 (PVB19), manifesting clinically as recurrent agranulocytosis and in bone marrow biopsy as recurrent pure granulocytic aplasia. Persistence of parvovirus infection was documented by the presence of PVB19 DNA and anti-PVB19-IgM antibodies in the serum fo...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1992.tb08894.x
更新日期:1992-02-01 00:00:00
abstract::The sera of 14 patients with quinine/quinidine-dependent thrombocytopenia were studied in the platelet suspension immunofluorescence test (PSIFT), the 51Cr-lysis assay and the complement fixation test (CFT). When anti-Ig or anti-IgG reagents were used, the PSIFT proved to be a little more sensitive than the 51Cr-lysis...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1982.tb02818.x
更新日期:1982-08-01 00:00:00
abstract::In four unrelated patients with chronic haemolysis and markedly reduced red blood cell (RBC) glutathione (49.5%, 12.6%, 11.5% and 15% of the normal concentration respectively), a severe glutathione synthetase (GSH-S, EC 6.3.2.3) deficiency was found. One case exhibited a neonatal haemolytic anaemia associated with oxo...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2141.2001.02526.x
更新日期:2001-02-01 00:00:00
abstract::New diagnostic criteria for the diagnosis of the various myelodysplastic syndromes (MDS) are proposed, and a detailed description is given of the features that may help define MDS. Five MDS are described: (1) refractory anaemia (RA), (2) RA with ring sideroblasts, (3) RA with excess of blasts (RAEB), (4) chronic myelo...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:
更新日期:1982-06-01 00:00:00
abstract::The platelet-sized particle formation in the human megakaryoblastic leukaemia cell line MEG-01 and its subline MEG-01s was examined. MEG-01 and MEG-01s cells spontaneously released platelet-sized particles into the culture medium, in which the cells occasionally extended cytoplasmic processes similar to those of megak...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.00576.x
更新日期:1998-02-01 00:00:00
abstract::Kidney iron deposition measured by R2* (magnetic resonance imaging) MRI is posited to result from tubular reabsorption of filtered haemoglobin due to intravascular haemolysis. In chronically transfused sickle cell disease (SCD), R2* is elevated and positively correlated with lactate dehydrogenase (LDH). To account for...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.17085
更新日期:2020-11-20 00:00:00
abstract::A primary analysis of the ASPIRE study found that the addition of carfilzomib to lenalidomide and dexamethasone (carfilzomib group) significantly improved progression-free survival (PFS) compared with lenalidomide and dexamethasone alone (control group) in patients with relapsed multiple myeloma (RMM). This post hoc a...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2017-05-01 00:00:00
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journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1994.tb04993.x
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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::The level of minimal residual disease (MRD) in marrow early in treatment strongly predicts outcome in childhood acute lymphoblastic leukaemia (ALL). Using PCR we studied 30 pairs of aspirates and trephines taken during induction treatment. Consensus PCR primers showed a monoclonal gene rearrangement in eight pairs, po...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:
更新日期:1998-10-01 00:00:00
abstract::Therapy with imatinib mesylate is limited by cellular resistance in chronic myeloid leukaemia (CML). Further, the limited availability of matching stem cell donors or an unfavourable risk profile for allogeneic stem cell transplantation (SCT) reduces the number of therapeutic options in a number of patients. To assess...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章
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更新日期:2004-01-01 00:00:00
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journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1978.tb01086.x
更新日期:1978-06-01 00:00:00
abstract::An 'artificial' plasma for one-stage factor-VIII assays is made by incubating human plasma with EDTA, to destroy factor VIII, and afterwards removing the anticoagulant by dialysis. Bovine factor V is then added to a given level. In the assay, contact activation is controlled by adding contact product. It was confirmed...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1978.tb05818.x
更新日期:1978-11-01 00:00:00
abstract::In acute lymphoblastic leukaemia (ALL), investigation of minimal residual disease by conventional morphology and immunology fails to detect levels of residual disease of < 1 leukaemic in 10-100 normal cells. The use of polymerase chain reaction (PCR) to exploit the diversity of the complementarity determining region (...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2141.1996.289831.x
更新日期:1996-01-01 00:00:00
abstract::The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia, immunodeficiency and eczema. X-linked thrombocytopenia (XLT) is a mild form of WAS with isolated thrombocytopenia. Both phenotypes are caused by mutation of the Wiskott-Aldrich syndrome protein (WASP) gene. In this ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1999.01694.x
更新日期:1999-11-01 00:00:00
abstract::Since glycoprotein IV (GPIV) has been shown to play an important role in the interaction of platelets with collagen and thrombospondin, the aggregation and secretion of GPIV-deficient platelets were examined. Using a binding assay with monoclonal 125I-OKM5 antibody against CD36 antigen and crossed immunoelectrophoresi...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1992.tb08177.x
更新日期:1992-05-01 00:00:00
abstract::The inoculation of L1210 or L5178Y leukaemia cells decreased the platelet count of the recipient mouse before extensive infiltration of marrow was expected by either tumour line. The decrease was more pronounced after intravenous inoculation of L1210 leukaemia than after intraperitoneal inoculation. Inoculation of L51...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1977.tb00608.x
更新日期:1977-03-01 00:00:00
abstract::The heterogeneity of pyruvate kinase (PK) deficiency associated with hereditary haemolytic anaemia is emphasized by studies of a kindred harbouring two distinct mutant forms of this enzyme, both of which were kinetically defective with markedly decreased affinities for the substrate, phosphoenolypyruvate. The two isoe...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1976.tb00174.x
更新日期:1976-09-01 00:00:00
abstract::Clinical and cytogenetic data were analysed in 54 patients with acute non-lymphocytic leukaemias (ANLL) or MDS (myelodysplastic syndromes) and deletion of the long arm of chromosome 7 (7q-), in order to determine if there is a commonly deleted region in 7q and to establish possible correlations between karyotypic feat...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1996.d01-2683.x
更新日期:1996-03-01 00:00:00
abstract::This study describes the effect of ferritin on lymphocyte function in vitro. Peripheral blood lymphocytes isolated from normal donors were incubated with purified human splenic ferritin, and the mitogenic effect of phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) and mixed lymphocyte reaction ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1979.tb01142.x
更新日期:1979-07-01 00:00:00
abstract::Severe neutropenia and protracted thrombocytopenia remain serious clinical problems following cord blood transplantation (CBT) due to the paucity of stem and progenitor cells in the grafts. Administration of ex-vivo expanded megakaryocyte progenitor cells may facilitate platelet production. We propose a novel strategy...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2009.08041.x
更新日期:2010-04-01 00:00:00