Abstract：
:Chronic myeloid leukaemia invariably progresses from a drug-sensitive to a drug-resistant, aggressive acute leukaemia. The mechanisms responsible for this are unknown, although loss of p53 has been reported in approximately 25% of cases. Elevated expression of Bcr-Abl is also associated with disease progression. We have shown that cells expressing high levels of Bcr-Abl also express elevated levels of p53 and the cell cycle inhibitor, p21WAF-1. Despite this, cells continue to cycle and are drug resistant. As p21WAF-1 inhibitory activity is associated with nuclear localization, we investigated its localization in Bcr-Abl-expressing cells, and found that it is predominantly cytoplasmic. We have also shown that it associates physically with the serine/threonine kinase AKT, but this association and the cytosolic location of p21WAF-1 are phosphinositide-3-kinase (PI3K) independent. Cytosolic p21WAF-1 has been reported to have a prosurvival role in other transformed cells. In Bcr-Abl-expressing cells, p21WAF-1 rapidly diminishes as the cells are sensitized to apoptosis, using the inhibitor STI571. It is possible therefore that p21WAF-1 could also have a positive, prosurvival role in these cells. This study suggests that, by retaining p21WAF-1 in a cytosolic location, Bcr-Abl can evade the cell cycle arrest normally induced by nuclear p21WAF-1 and therefore also enable the cells to negate an important feature of a tumour suppressor response.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Keeshan K,Cotter TG,McKenna SLdoi
10.1046/j.1365-2141.2003.04538.xsubject
Has Abstractpub_date
2003-10-01 00:00:00pages
34-44issue
1eissn
0007-1048issn
1365-2141pii
4538journal_volume
123pub_type
杂志文章abstract：:The tumour suppressor TP53 (previously termed p53) mediates a pathway that is considered to be one of the most important mechanisms in the maintenance of genomic stability. The function of TP53 can be abrogated by genomic deletion, mutation, or deregulation of upstream and downstream participants in the TP53 pathway. ...
journal_title：British journal of haematology
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2141.2009.07739.x
更新日期：2009-08-01 00:00:00
abstract：:In the last few years, mutations that cause disease through increased efficiency of mRNA translation have been discovered. Hereditary hyperferritinaemia-cataract syndrome (HHCS) arises from various point mutations or deletions within the iron-responsive element (IRE) in the 5'-UTR of the L-ferritin mRNA. Each unique m...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1046/j.0007-1048.2001.03310.x
更新日期：2002-03-01 00:00:00
abstract：:Screening of the skeleton by plain radiography was compared to magnetic resonance imaging (MRI) of the lumbar spine in 41 patients with multiple myeloma. In the lumbar spine, myeloma lesions were detected in 15 patients with radiography and in 28 patients with MRI. Radiography of the lumbar spine was not positive in a...
journal_title：British journal of haematology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2141.1995.tb05363.x
更新日期：1995-11-01 00:00:00
abstract：:The role of antiphospholipid antibodies in the pathogenesis of the thrombocytopenia observed during primary antiphospholipid antibody syndrome (APAS) and systemic lupus erythematosus (SLE) remains controversial. We have used the MAIPA test to examine the frequency and specificity of anti-platelet antibodies directed a...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1046/j.1365-2141.1997.2243038.x
更新日期：1997-08-01 00:00:00
abstract：:The use of peripheral blood stem cells instead of bone marrow as the source of haemopoietic cells for allogeneic transplantation is being increasingly explored. We have analysed data from 17 normal donors who underwent stem cell mobilization for allogeneic transplantation with an identical protocol using G-CSF at a do...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1046/j.1365-2141.1996.d01-1897.x
更新日期：1996-11-01 00:00:00
abstract：:Anti-cardiolipin antibody (aCL) measurement is only semi-reproducible, and current assays detect irrelevant as well as clinically significant antibodies. Factors found to influence results included the source of the enzyme-linked immunoabsorbent assay (ELISA) plate, and its pretreatment with solvents; the nature of th...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1046/j.1365-2141.1998.00532.x
更新日期：1998-01-01 00:00:00
abstract：:We describe a patient with a 9-year history of thrombotic thrombocytopenic purpura (TTP) who exhibited four relapses. Intravenous immunoglobulin (IVIg) was effective for these four episodes. The patient was well and the laboratory findings were within normal ranges between each episode, although unusually large von Wi...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1046/j.1365-2141.2000.01930.x
更新日期：2000-03-01 00:00:00
abstract：:The sensitivity of populations of human granulocyte precursors to factors with colony stimulating activity (CSA) was assessed in agar culture in vitro. The mean threshold of stimulation was estimated by analysis of dose-response curves of clone growth against concentration of CSA. This method of assessment has the adv...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1111/j.1365-2141.1979.tb05892.x
更新日期：1979-04-01 00:00:00
abstract：:Globin-gene mapping of DNA from 13 families with normal Hb A2 beta-thalassaemia (both type 1 and type 2) failed to detect any difference from normal in their globin-gene arrangement. We conclude that deletions such as those responsible for gamma beta-thalassaemia or a 'silent' Hb Lepore are not responsible for this ty...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1111/j.1365-2141.1982.tb07289.x
更新日期：1982-05-01 00:00:00
abstract：:The US National Cancer Institute's Surveillance, Epidemiology and End Results program was used to develop aetiological clues for hairy cell leukaemia (HCL). Descriptive techniques (age-adjusted incidence trends, age-specific incidence rates (IR), and age distributions-at-diagnosis) were supplemented with mathematical ...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1111/j.1365-2141.2008.07156.x
更新日期：2008-07-01 00:00:00
abstract：:We have identified the beta-thalassaemia alleles in nearly all known Turkish Cypriot beta-thalassaemia homozygotes and in over 700 Greek Cypriot beta-thalassaemia heterozygotes living on the island of Cyprus. The data confirmed earlier observations that the IVS-I-100 (G-->A) mutation is present for about 74-80%, while...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1111/j.1365-2141.1992.tb03000.x
更新日期：1992-08-01 00:00:00
abstract：:The profile of thymidine kinase isoenzymes was determined in peripheral blood lymphocytes from 14 patients with chronic lymphocytic leukaemia (CLL) and 31 controls. Twelve patients with indolent disease showed TK2 isoenzyme activity, while two patients in whom the disease evolved and two patients who presented with ag...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1111/j.1365-2141.1981.tb07251.x
更新日期：1981-11-01 00:00:00
abstract：:A 2-year-old girl is described with severe haemophilia A (factor VIII: C < 0.01 units/ml). Both of her parents were phenotypically normal. Cytogenetic analysis on the proband demonstrated an interstitial X chromosome deletion encompassing Xq26-q28. Molecular studies with several polymorphic markers close to and within...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1111/j.1365-2141.1995.tb05213.x
更新日期：1995-08-01 00:00:00
abstract：:Chemokines are a family of over 40 small (8 kDa) related proteins with the function of moving cells along a chemotactic gradient, either to organise cells within an organ or to facilitate the movement of leucocytes around the body. Mouse models have implicated the importance of the chemokine CXCL12 in haematopoiesis a...
journal_title：British journal of haematology
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2141.2005.05841.x
更新日期：2006-02-01 00:00:00
abstract：:We investigated the use of a new conditioning regimen followed by allogeneic bone marrow transplantation (BMT) for treating children with acute lymphoblastic leukaemia (ALL) after relapse within 6 months of the completion of therapy. One hundred and sixteen children with acute lymphoblastic leukaemia in second or subs...
journal_title：British journal of haematology
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1046/j.1365-2141.1998.00825.x
更新日期：1998-08-01 00:00:00
abstract：:Smouldering multiple myeloma (SMM) presents without MM defining symptoms. We aimed to identify patients with SMM with an 80% risk of progression within 2 years using only serum parameters. In total, 527 patients with SMM were included and divided into a training group (287 patients from the Czech Myeloma Group [CMG]) ...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1111/bjh.16572
更新日期：2020-07-01 00:00:00
abstract：:A new putative hepatitis virus has recently been discovered and termed GB virus C (GBV-C). We investigated the prevalence of this virus among 50 haemophiliacs treated with non-virus-inactivated clotting factor concentrates prior to 1985 and 21 haemophiliacs treated exclusively with virus-inactivated clotting factor co...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1046/j.1365-2141.1997.4883292.x
更新日期：1997-12-01 00:00:00
abstract：:A case of acute myeloid leukaemia (AML) occurring in a patient with untreated chronic lymphatic leukaemia (CLL) is presented. The diagnosis of two simultaneous leukaemic processes is based on morphological, cytochemical and immunological findings. The significance of the development of AML in patients with CLL is disc...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1111/j.1365-2141.1979.tb03764.x
更新日期：1979-11-01 00:00:00
abstract：:As the cure rates for haematological malignancies have improved, the exploration of the balance between efficacy and side effects has become a major research target. The antifolate methotrexate is widely used in the treatment of acute lymphoblastic leukaemia, non-Hodgkin lymphoma, and osteosarcoma. Even when given ide...
journal_title：British journal of haematology
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2141.2009.07765.x
更新日期：2009-09-01 00:00:00
abstract：:Treatment with intravenous recombinant human interleukin-2 (rh IL-2) is frequently accompanied by the capillary leak syndrome and disturbances of the coagulation system. Although the exact mechanisms are still not fully understood, the involvement of the endothelium is proven. This investigation aimed to elucidate mor...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1046/j.1365-2141.1999.01453.x
更新日期：1999-06-01 00:00:00
abstract：:A stroma free platelet lysate supernatant (PLS) was prepared by repeatedly freezing and thawing a human platelet suspension separated from platelet rich plasma by gel filtration. The material was potently thrombogenic in a stasis model in rabbits, but only when combined with a purified preparation of factor Xa. The do...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1111/j.1365-2141.1982.tb02803.x
更新日期：1982-07-01 00:00:00
abstract：:Platelet aggregation is commonly used to investigate patients with possible dense granule storage pool deficiency (delta SPD), but recent studies have shown that this investigation is not specific or sensitive for this disorder. We describe a simple one-step technique to detect mepacrine loaded platelets by flow cytom...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1111/j.1365-2141.1995.tb08901.x
更新日期：1995-01-01 00:00:00
abstract：:The role of factor XI (FXI) in blood coagulation has been clarified in recent years by descriptions of FXI-deficient patients who are prone to excessive bleeding after haemostatic challenge. We have studied a large kindred of an Italian FXI-deficient patient with a previously undescribed mutation. The propositus, a 68...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1046/j.1365-2141.1999.01150.x
更新日期：1999-01-01 00:00:00
abstract：:Cross-species Northern blot hybridization and radioimmunoassay have provided evidence for the expression of an erythropoietin (EPO)-like gene in the rainbow trout. The principal site of EPO-like mRNA and antigen expression in the adult trout appears to be the kidney which also acts as the major erythropoietic organ. T...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1111/j.1365-2141.1995.tb03406.x
更新日期：1995-05-01 00:00:00
abstract：:Twenty-seven stable subclones of seven independent cellular hybrids producing murine monoclonal antibodies to human von Willebrand factor (vWF) have been established. The specificity of the hybridoma antibodies for vWF has been substantiated by a variety of methods including binding to highly purified vWF, absence of ...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1111/j.1365-2141.1984.tb02937.x
更新日期：1984-08-01 00:00:00
abstract：:MPLW515L/K and JAK2V617F can co-exist in myelofibrosis with myeloid metaplasia (MMM). The chronology of clonal emergence was studied in three such cases using serially stored bone marrow. At diagnosis, a major MPL515 mutant clone was accompanied by a minor JAK2V617F clone in all three instances. At 25 time points over...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1111/j.1365-2141.2006.06348.x
更新日期：2006-12-01 00:00:00
abstract：:Since cardiotoxicity is a life threatening late effect, a reduction of cardiotoxicity in the treatment of acute myeloid leukaemia (AML) is essential. This review is a compilation of the current knowledge about cardiotoxicity after AML treatment and of how future directions in treatment may affect its incidence. A tota...
journal_title：British journal of haematology
pub_type： 杂志文章,评审
doi：10.1111/bjh.14374
更新日期：2016-11-01 00:00:00
abstract：:Human blood platelets were stored in autologous plasma at 4 degrees C or 22 degrees C and their surface changes were probed with three lectins--wheat germ agglutinin, lentil lectin and concanavalin A. Platelets stored at either temperature for different times showed increased sensitivity to lectins. Lectins which were...
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1111/j.1365-2141.1988.tb02436.x
更新日期：1988-09-01 00:00:00
abstract：:We report stability of a clonal immunoglobulin heavy chain (IgH) gene rearrangement in a case of childhood acute lymphoblastic leukaemia (ALL) relapsing 17 years after completion of first-line therapy. Clonal stability was shown by polymerase chain reaction amplification of the hypervariable CDRIII region of IgH gene....
journal_title：British journal of haematology
pub_type： 杂志文章
doi：10.1046/j.1365-2141.1997.3103129.x
更新日期：1997-09-01 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
