Abstract:
:Novel therapies with increased efficacy and decreased toxicity are desperately needed for the treatment of acute myeloid leukaemia (AML). The anti CD33 immunoconjugate, gemtuzumab ozogamicin (GO), was withdrawn with concerns over induction mortality and lack of efficacy. However a number of recent trials suggest that, particularly in AML with favourable cytogenetics, GO may improve overall survival. This data and the development of alternative novel monoclonal antibodies (mAb) have renewed interest in the area. Leukaemic stem cells (LSC) are identified as the subset of AML blasts that reproduces the leukaemic phenotype upon transplantation into immunosuppressed mice. AML relapse may be caused by chemoresistant LSC and this has refocused interest on identifying and targeting antigens specific for LSC. Several mAb have been developed that target LSC effectively in xenogeneic models but only a few have begun clinical evaluation. Antibody engineering may improve the activity of potential new therapeutics for AML. The encouraging results seen with bispecific T cell-engaging mAb-based molecules against CD19 in the treatment of B-cell acute lymphobalstic leukaemia, highlight the potential efficacy of engineered antibodies in the treatment of acute leukaemia. Potent engineered mAb, possibly targeting novel LSC antigens, offer hope for improving the current poor prognosis for AML.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Gasiorowski RE,Clark GJ,Bradstock K,Hart DNdoi
10.1111/bjh.12691subject
Has Abstractpub_date
2014-02-01 00:00:00pages
481-95issue
4eissn
0007-1048issn
1365-2141journal_volume
164pub_type
杂志文章,评审abstract::We investigated the effects of Il-12 on functional properties of CD3+ CD8+ granular lymphocytes (GL) of of patients with lymphoproliferative disease of granular lymphocytes (LDGL). To this aim, in 10 cases with clonal CD3+ GL proliferation (nine cases with an associated TCR alpha/beta receptor and one case with a TCR ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1996.d01-1495.x
更新日期:1996-02-01 00:00:00
abstract::Polycythaemia vera (PV) patients have an overall comparatively favourable prognosis, but disease progression is very heterogeneous and life-threatening thrombosis and bleedings are frequent complications in untreated disease. Moreover, transformation to more severe secondary myelofibrosis and acute myeloid leukaemia c...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.16450
更新日期:2020-06-01 00:00:00
abstract::The two major epidemiological clues to the pathogenesis of Burkitt lymphoma (BL) are the geographical association with malaria--BL incidence relates to the malaria transmission rate--and early infection by Epstein-Barr virus (EBV). Both agents cause B cell hyperplasia, which is almost certainly an essential component ...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2141.2011.09013.x
更新日期:2012-03-01 00:00:00
abstract::We evaluated the feasibility of collecting peripheral blood progenitor cells (PBPC) in patients with acute myeloid leukaemia (AML) following two cycles of induction chemotherapy with idarubicin, cytarabine and etoposide (ICE), and one cycle of consolidation therapy with high-dose cytarabine and mitoxantrone (HAM). Thi...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1997.3933207.x
更新日期:1997-11-01 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::Two cases of Ph1-positive chronic granulocytic leukaemia with hitherto undescribed translocations are presented. In case 1 the deleted part of chromosome number 22q- was translocated to the short arm of the X chromosome, t(X;22)(p22;q11). Pronounced basophilia, trisomy 19 in the majority of metaphases, and a partial c...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1979.tb05847.x
更新日期:1979-02-01 00:00:00
abstract::Cardiopulmonary bypass (CPB) induces a bleeding defect which leads to enhanced blood loss. A double-blind study was carried out comparing aprotinin with placebo in patients undergoing re-operation for heart valve replacement. The results confirm that aprotinin is effective at reducing such loss. In the placebo treated...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2141.1993.tb03344.x
更新日期:1993-11-01 00:00:00
abstract::The polymerase chain reaction (PCR) assay was used to detect human parvovirus B19 DNA in 38 blood products and start plasma pools from five different manufacturers. The products examined were albumin, factor VIII, intravenous (i.v.) and intramuscular (i.m) immunoglobulin batches. The majority of pools from all the man...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1996.d01-1679.x
更新日期:1996-06-01 00:00:00
abstract::The proviral copy (PVC) number in peripheral blood mononuclear cells (PBMCs) of human immunodeficiency virus (HIV)-infected individuals was measured by a quantitative polymerase chain reaction (PCR) assay to determine over time the relation between the viral load and the evolution towards the disease in HIV-infected p...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1992.tb06446.x
更新日期:1992-10-01 00:00:00
abstract::Globin synthesis was studied in four Negro families including 10 members with Hb A-HPFH and four with Hb S-HPFH. The beta/alpha specific activity ratios in 10 of these HPFH heterozygotes were similar to those of the control group. In two patients with Hb A-HPFH, the beta/alpha ratio was slightly decreased in one (0.84...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1976.tb00939.x
更新日期:1976-03-01 00:00:00
abstract::Minimal residual disease (MRD) in acute myeloid leukaemia (AML) poses a major challenge due to drug insensitivity and high risk of relapse. Intensification of chemotherapy and stem cell transplantation are often pivoted on MRD status. Relapse rates are high even with the integration of first-generation FMS-like tyrosi...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.16665
更新日期:2020-10-01 00:00:00
abstract::Human umbilical vein endothelial cells (HUVEC) in primary confluent cultures lost their normal polygonal shape and assumed a 'contracted' appearance as judged by phase contrast microscopy when exposed to highly purified bovine thrombin (2 N.I.H. u/ml). Total actin in thrombin-exposed cells did not differ from that of ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1984.tb06108.x
更新日期:1984-12-01 00:00:00
abstract::Monoclonal gammopathy of undetermined significance (MGUS) has been associated with an increased risk of thrombosis. We carried out a retrospective multicentre cohort study on 1491 patients with MGUS. In 49 patients (3.3%) MGUS was diagnosed after a thrombotic event. Follow-up details for a period of at least 12 months...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/bjh.12168
更新日期:2013-03-01 00:00:00
abstract::In type 1 Gaucher disease a bleeding tendency occurs which is partly caused by thrombocytopenia due to massive splenomegaly. In addition, low levels of factors IX and XI have been described. The mechanism responsible for these clotting factor abnormalities is unknown. We performed a detailed study of parameters of coa...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1997.d01-2076.x
更新日期:1997-03-01 00:00:00
abstract::Venesection of 10% of whole blood volume or plateletpheresis was performed in nine patients with chronic myeloproliferative disorders and in five normal control subjects. Before venesection, the patients showed impaired platelet aggregation in 33% of tests, most often in response to stimulation with 9 mumol adrenaline...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1978.tb03629.x
更新日期:1978-08-01 00:00:00
abstract::Duffy blood group antigens are carried on a glycoprotein that is predicted to pass through the erythrocyte membrane seven times and is a promiscuous chemokine receptor. The Fy(a- b-) phenotype is present in two-thirds of African-American Blacks but is rare in Caucasians. In Blacks, the phenotype is due to a non-functi...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.01882.x
更新日期:2000-02-01 00:00:00
abstract::Heparin-induced thrombocytopenia (HIT) is mediated by a heparin-dependent antibody/platelet factor 4/heparin complex binding to platelets via the Fc gamma receptor (type IIA). A single base polymorphism at position 131 of Fc gamma RIIA changes the native arginine to histidine. In the presence of murine monoclonal IgG1...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1995.tb05383.x
更新日期:1995-11-01 00:00:00
abstract::In order to clarify the indications for splenectomy in patients with homozygous beta thalassaemia we studied, retrospectively, the basal pre-transfusion haemoglobin levels and blood transfusion requirements before and after splenectomy, in a series of patients with this disorder. Thirty-six patients, of whom 20 underw...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1975.tb00870.x
更新日期:1975-11-01 00:00:00
abstract::A patient with Jo-1 antibody-associated polymyositis (Jo-1 PM) had a Karnofsky score of 40% and severe muscle, liver and lung damage that was refractory to standard therapy. The female patient received an autologous T-cell-depleted haematopoietic stem cell transplant (HSCT) after myeloablative conditioning. The transp...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.02191.x
更新日期:2000-08-01 00:00:00
abstract::Bone loss in multiple myeloma (MM) is caused by an uncoupling of bone formation to resorption trigged by malignant plasma cells. Increasing evidence indicates that the bone remodelling compartment (BRC) canopy, which normally covers the remodelling sites, is important for coupled bone remodelling. Loss of this canopy ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.13584
更新日期:2015-11-01 00:00:00
abstract::The Brown Norwegian rat transplanted with promyelocytic leukaemic cells (BNML) has been used as a model for human acute myeloid leukaemia. We have previously shown that both the blood supply to the bone marrow and the metabolic rate decrease in relation to the leukaemic development in these rats. Here we have investig...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.00801.x
更新日期:1998-07-01 00:00:00
abstract::An increase in bone marrow blood flow has been previously described in anaemic rabbits and dogs. We examined the effect of haemorrhage and haemolysis in female Sprague-Dawley rats, with the hypothesis that high blood flow was related to hyperplasia of bone marrow tissue and that the increase would affect bone as well....
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1990.tb06343.x
更新日期:1990-04-01 00:00:00
abstract::This communication reports a patient with concomitant expansions of CD4+ and CD8+ large granular lymphocytes. Immunological analyses revealed that the abnormally increased CD4+ LGL fraction was phenotypically similar to other reported persistent CD4+ LGL expansions, whereas the phenotypic profile for the CD8+ LGL comp...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1994.tb05087.x
更新日期:1994-11-01 00:00:00
abstract::The induction of anaemia and reticulocytosis by arylhydrazines was influenced by substituents on the benzene ring of phenylhydrazine. Arylhydrazines with ortho substituents, which would hinder the binding by haemoglobin of a ligand derived from the arylhydrazine, resulted in the least anaemia and reticulocytosis. Thes...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1976.tb01879.x
更新日期:1976-01-01 00:00:00
abstract::The administration of Interleukin-2 (IL-2) causes the release or generation of other cytokines such as tumour necrosis factor (TNF) which, by disturbing the anticoagulant properties of the endothelium, may induce a procoagulant state in patients receiving this drug. We therefore evaluated the effects of IL-2 on coagul...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1992.tb06421.x
更新日期:1992-10-01 00:00:00
abstract::Serum antiplatelet IgG and platelet-associated IgG (PAIgG) were studied in 68 AIDS-free human immunodeficiency virus (HIV)-infected patients with severe immunologic thrombocytopenic purpura (ITP), for the presence of platelet autoantibodies. Serum IgG with antiplatelet activity was found in 72% of the sera. However, t...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1989.tb00259.x
更新日期:1989-10-01 00:00:00
abstract::A recombinant bispecific single-chain fragment variable antibody (bsscFv), directed against the B-cell antigen CD19 and the low affinity Fc-receptor FcgammaRIII (CD16), was designed for use in the treatment of patients with leukaemias and lymphomas. The Fc-portions of whole antibodies were deliberately eliminated in t...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2005.05414.x
更新日期:2005-07-01 00:00:00
abstract::Limited tryptic digestion of native spectrin (Sp) has revealed several variants in hereditary pyropoikilocytosis (HPP) and in a subset of patients with hereditary elliptocytosis (HE). In most cases, tryptic peptide corresponding to the alpha I (N-terminal) 80 kD domain is wholly or partially replaced by smaller fragme...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1990.tb06376.x
更新日期:1990-11-01 00:00:00
abstract::Selinexor, an oral Selective Inhibitor of Nuclear Export, targets Exportin 1 (XPO1, also termed CRM1). Non-clinical studies support combining selinexor with proteasome inhibitors (PIs) and corticosteroids to overcome resistance in relapsed/refractory multiple myeloma (RRMM). We conducted a phase I dose-escalation tria...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/bjh.15969
更新日期:2019-08-01 00:00:00
abstract::The use of 111Indium oxine as a platelet label for the performance of platelet life-span studies has been examined. Platelet life-span in normal subjects varied between 8 X 10 and 10 X 36 d. Patients with primary thrombocythaemia had clearly reduced platelet life-span whether or not they presented with vascular occlus...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1984.tb06115.x
更新日期:1984-12-01 00:00:00