Abstract:
:Mutations of the p53 tumour suppressor gene occur in 20% of chronic myeloid leukaemia (CML) patients in blastic crisis, but it is still uncertain whether this inactivation plays a role in the pathogenesis of blastic transformation or in maintaining the leukaemic proliferation in CML, as it does in several solid tumours. We have previously shown that more than 50% of both normal and CML CD34+ cells express the p53 protein. However, haemopoietic cells at different phases of the cell cycle express p53 with different conformations, suggesting that the function of p53 may be closely regulated during the cell cycle. In order to elucidate the mechanism by which p53 suppresses cell proliferation, we evaluated the effects of inhibiting p53 expression on cell cycle and cell kinetics of chronic phase CML (n = 12) and normal (n = 7) bone marrow light-density cells and purified CD34+ progenitors by using an 18-mer modified antisense oligonucleotide which targets the region covering the six base pairs immediately before the first codon and the first four coding codons of p53. We found that the number of cells positive for the cell cycle-specific nuclear antigen Ki67 and for the BrdU monoclonal antibody (McAb) was significantly increased after p53 antisense olignucleotide treatment. At the same time, p53 protein expression was completely abrogated in both light-density and CD34+ cells. In addition, DNA analysis by flow cytometry demonstrated that the number of cells in quiescent phases of the cell cycle (G0-G1) was significantly decreased after exposure of light-density cells to p53 antisense oligomers, whereas the number of cells in S or G2-M phases was increased. Furthermore, the longer the incubation time the higher the increase in cell proliferation. Treatment of CML, cells with p53 antisense oligomers also resulted in significantly increased numbers of CFU-GM colonies. Our data suggest that p53 is a negative regulator of cell proliferation and its action is mediated through changes in cell cycle kinetics, mainly before the S phase. We can further speculate that the loss of p53 function, at the time of blastic crisis of CML, may play a role, in combination with other genetic changes (p210 BCR/ABL, Rb gene abnormality, others to be defined), in inducing disturbances in cell proliferation, differentiation, and apoptosis.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Lanza F,Bi S,Moretti S,Castoldi G,Goldman JMdoi
10.1111/j.1365-2141.1995.tb03374.xsubject
Has Abstractpub_date
1995-05-01 00:00:00pages
8-14issue
1eissn
0007-1048issn
1365-2141journal_volume
90pub_type
杂志文章abstract::In spite of several studies of immunoglobulin (Ig) gene rearrangements in whole Hodgkin's disease (HD) tissues and in isolated single Reed-Sternberg (RS) cells, the issue of clonality of the RS cell in HD remains incompletely resolved. Analysis of X-chromosome inactivation patterns (XCIPs) can be used to determine whe...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1999.01727.x
更新日期:1999-12-01 00:00:00
abstract::Imatinib mesylate (IM, STI 571, Glivec) can induce a high rate of complete cytogenetic response (CCR) in chronic myeloid leukaemia (CML) patients, although to date the majority of patients continue to have detectable disease by sensitive reverse transcription polymerase chain reaction (RT-PCR). It is therefore possibl...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2003.04599.x
更新日期:2003-11-01 00:00:00
abstract::Risk factors for acute graft-versus-host disease (GvHD) remain controversial. We performed uni- and multivariate statistical analyses on a series of 37 patients receiving a non-depleted allogeneic bone marrow transplant from an HLA-identical sibling donor for a haematological malignancy, in order to identify risk fact...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1988.tb02508.x
更新日期:1988-12-01 00:00:00
abstract::The pathogenesis of HELLP (haemolysis, elevated liver enzyme and low platelet count) syndrome, a severe presentation of pre-eclampsia, is still an enigma. Activated protein C resistance resulting from a mutation in coagulation factor V has recently emerged as the leading cause of thrombosis in pregnancy. We report on ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1996.410947.x
更新日期:1996-03-01 00:00:00
abstract::We examined the in vivo effects and safety of the third generation bisphosphonate, zoledronate (ZOL) alone and combined with imatinib mesylate against primary Philadelphia chromosome positive (Ph+) leukaemic cells. ZOL inhibited the prenylation of Rap1A in leukaemic cells in vitro and synergised with imatinib to enhan...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2005.05648.x
更新日期:2005-08-01 00:00:00
abstract::Two single-nucleotide substitutions in PKLR constituted the molecular basis underlying pyruvate kinase (PK) deficiency in a patient with severe haemolytic anaemia. One novel mutation, IVS5+1G>A, abolished the intron 5 donor splice site. The other mutation, c.1436G>A, altered the intron 10 donor splice site consensus s...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2004.04895.x
更新日期:2004-04-01 00:00:00
abstract::2-3-Dihydroxybenzoic acid was evaluated as a potentially useful, orally effective iron-chelating drug by performing iron balance studies in patients with beta-thalassaemia major. The administration of this substance at 25 mg/kg/d to five patients for 8 d caused an average increase in iron excretion of 4.5 mg/d. When t...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1976.tb03566.x
更新日期:1976-08-01 00:00:00
abstract::Neutralizing anti-IFN alpha antibodies (nIFN alpha Abs) occur in a significant proportion of patients with hairy cell leukaemia, hepatitis or solid tumours treated with recombinant IFN alpha (IFN alpha 2a or IFN alpha 2b), but information on their incidence in chronic myeloid leukaemia (CML) is scanty and their clinic...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1996.d01-1790.x
更新日期:1996-08-01 00:00:00
abstract::Increasing use of direct oral anticoagulants (DOACs) has made management of non-valvular atrial fibrillation and venous thromboembolism easier in most patients. But the presence of co-existing renal impairment could render the use of DOACs problematic because all of these drugs have varying degrees of renal excretion....
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/bjh.15564
更新日期:2018-10-01 00:00:00
abstract::Although many cases of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are cytogenetically normal, interphase fluorescence in situ hybridization (FISH) analyses reveal aberrations in the majority of the cases. Most likely, non-neoplastic cells are more prone to divide in culture tha...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2004.05060.x
更新日期:2004-08-01 00:00:00
abstract::The localization of adenylate cyclase (AC) in rat bone marrow was studied at the ultrastructural level using a cytochemical technique with adenosine triphosphate (ATP) as substrate. The strongest precipitate occurred around cytoplasmic membranes of cells of granulocytic lineage. Around cells of erythrocytic lineage, a...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1984.tb03988.x
更新日期:1984-11-01 00:00:00
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::Bone disease in patients with thalassaemia major is a multifactorial and still poorly understood process. The present study evaluated 45 thalassaemic patients using dual X-ray absorptiometry at three sites (lumbar spine, head of femur and forearm) to assess bone mineral density, in parallel with a series of biochemica...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2001.02549.x
更新日期:2001-01-01 00:00:00
abstract::Myelofibrosis with myeloid metaplasia (MMM) is uniquely characterized by macroscopic bone marrow stromal changes that are believed to be both reactive and cytokine mediated. Furthermore, a prognostically detrimental increase in bone marrow angiogenesis has recently been demonstrated. These observations suggest a poten...
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.1365-2141.2002.03443.x
更新日期:2002-05-01 00:00:00
abstract::The molecular defect of a congenitally dysfunctional form of prothrombin, prothrombin Obihiro, was identified in a patient with a severe bleeding tendency. He showed reduced fibrinogen clotting activity, despite a normal prothrombin antigen level. Nucleotide sequencing of amplified DNA revealed a C-->T change at nucle...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1995.tb05601.x
更新日期:1995-07-01 00:00:00
abstract::Shwachman-Diamond Syndrome (SDS) is a multi-system genetic disorder with bone marrow failure. SBDS, the gene associated with SDS, has been postulated to play a role in ribosome biogenesis and RNA processing, but its functions are still unknown. To study whether these pathways are interrupted when Sbds protein is lost,...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2009.07692.x
更新日期:2009-06-01 00:00:00
abstract::A digital image processing technique has been used to quantitate bone marrow fibre in histological material (both biopsy and necropsy) from 17 cases of myelofibrosis. An attempt was made to correlate the results of these measurements with other diagnostically relevant parameters. Bone marrow fibre was found to correla...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1979.tb03697.x
更新日期:1979-05-01 00:00:00
abstract::Pralatrexate inhibits folic acid metabolism, and preclinical studies have shown that it is cytotoxic to multiple myeloma cells. This phase 1 study investigated the safety and efficacy of pralatrexate in combination with bortezomib in adults with relapsed or refractory multiple myeloma. A standard 3 + 3 design was used...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.13946
更新日期:2016-04-01 00:00:00
abstract::This study was designed to investigate the ability of long-term primary cultures of adult human hepatocytes to secrete the main haemostasis proteins. Factors II, V, VII, VIII, PIVKA-II (protein induced by vitamin K 1 absence or antagonist II), fibrinogen and antithrombin were quantified in culture medium by immunologi...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2004.04957.x
更新日期:2004-06-01 00:00:00
abstract::Following a recent court judgment, legal and moral issues surrounding consent have been thrown into the spotlight. Elizabeth Larner, Solicitor, and Rachel Carter, Partner, of Wollen Michelmore LLP, look at the issues surrounding consent, including where problems arise in the fields of clinical negligence and non-accid...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/bjh.13795
更新日期:2016-01-01 00:00:00
abstract::Treatment with 75 microg/kg/d intravenous (i.v.) anti-D was compared with 50 microg/kg/d in a prospective randomized study of 27 RhD-positive, human immunodeficiency virus-negative, adult, acute, non-splenectomized patients with immune thrombocytopenic purpura (ITP) and platelet counts < or = 30 x 109/l. The higher do...
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.1365-2141.2001.02627.x
更新日期:2001-03-01 00:00:00
abstract::The bcl-2 gene is rearranged in most cases of follicular lymphoma and the breakpoint clusters into two specific regions: mbr and mcr. Rearrangements to immunoglobulin heavy chain genes (IgH) result in a deregulation of the gene and increased transcription of mRNA for the bcl-2 protein. In chronic lymphocytic leukaemia...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1996.00388.x
更新日期:1996-03-01 00:00:00
abstract::The anti-cancer drug arsenic trioxide (AT) induces apoptosis in a variety of transformed or proliferating cells. However, little is known regarding its ability to induce apoptosis in terminally differentiated cells, such as neutrophils. Because neutropenia has been reported in some cancer patients after AT treatment, ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2005.05866.x
更新日期:2006-02-01 00:00:00
abstract::Association between HLA haplotypes and long survival was investigated in 116 children with acute lymphoblastic leukaemia. It was found that patients with A2 B12 and/or A2 B40 haplotypes survived longer than patients wtihout these two haplotypes. Since all children were treated with transfer factor obtained from their ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1980.tb01206.x
更新日期:1980-02-01 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::Phosphatidylserine (PS) externalization may contribute to Sickle Cell Disease (SCD) characteristics including thrombogenesis, endothelial adhesion and shortened red blood cell (RBC) lifespan. Aminophospholipid translocase (APLT) returns externalized PS to the inner membrane, and phospholipid scramblase (PLSCR) equilib...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2009.07760.x
更新日期:2009-08-01 00:00:00
abstract::Dogs affected with cyclic haematopoiesis (CH) and experiencing recurrent 12-day cycles of neutropenia were supralethally irradiated and transplanted with marrow from their normal littermates. Following transplantation of the normal marrow, dogs with CH experienced no further cycles of neutropenia. Platelet and reticul...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1975.tb00535.x
更新日期:1975-06-01 00:00:00
abstract::Increasing numbers of patients are surviving after allogeneic bone marrow transplantation and are therefore at risk for developing late complications. Among these complications, avascular necrosis of bone has been reported, but only two single-centre studies included sufficient patients to enable analysis of the risk ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1997.1262940.x
更新日期:1997-06-01 00:00:00
abstract::The transforming growth factor-beta-related factor bone morphogenetic protein 4 (BMP4) is expressed in the human embryonic aorta-gonad-mesonephros (AGM) coincident with the emergence of haematopoietic cells and influences postnatal mammalian haematopoietic stem cells in vitro. To investigate the role of BMP4 in mammal...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2007.06795.x
更新日期:2007-10-01 00:00:00
abstract::Minimal residual disease (MRD) assessments were performed retrospectively after allogeneic stem cell transplantation (SCT) in 32 patients (23 children and nine adults) with acute lymphoblastic leukaemia (ALL). Using immunoglobulin and T-cell receptor rearrangements as clonal markers, MRD was detected after SCT in nine...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2003.04495.x
更新日期:2003-09-01 00:00:00