Abstract:
:Recurrent large-scale somatic copy number alterations (SCNAs), and somatic point mutations can be analysed to stratify patients with chronic lymphocytic leukaemia (CLL) into distinct prognostic groups. To investigate the relationship between SCNAs and somatic mutations, we performed whole-exome sequencing and single nucleotide polymorphism microarray analyses on 98 CLL patients from 40 families with a high burden of CLL. Overall, 69 somatic mutations in 29 CLL driver genes were detected among 45 subjects (46%), with the most frequently mutated genes being TP53 (8·2%), NOTCH1 (8·2%) and ATM (5·1%). Additionally, 142 SCNAs from 54 subjects (57%) were detected, including losses of chromosome 13q14 (28·9%), 11q (5·6%), 17p (2·1%), and gain of chromosome 12 (4·2%). We found that patients having both an adverse point mutation in a CLL driver gene and an unfavourable SCNA tended to have poorer survival (Hazard ratio [HR] = 3·17, 95% confidence interval [CI] = 0·97-10·35; P = 0·056) than patients having either a point mutation (HR = 1·34, 95%CI = 0·66-2·71; P = 0·42) or SCNAs (HR = 2·65, 95%CI = 0·77-9·13; P = 0·12). TP53 mutation carriers were associated with the poorest overall survival (HR = 4·39, 95%CI = 1·28-15·04; P = 0·018). Our study suggests that combining SCNA and mutational data could contribute to predicting outcome in familial CLL.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Zhou W,Goldin L,Wang M,McMaster ML,Jones K,Burdett L,Chanock SJ,Yeager M,Dean M,Caporaso NEdoi
10.1111/bjh.15239subject
Has Abstractpub_date
2018-06-01 00:00:00pages
604-613issue
5eissn
0007-1048issn
1365-2141journal_volume
181pub_type
杂志文章abstract::The success of genetically engineered T cells that express chimeric antigen receptors (CARTs) has been a momentous step forward in harnessing the potent cancer fighting abilities of the immune system. The efficacy seen in relapsed/refractory (r/r) acute lymphoblastic leukaemia (ALL), not only by inducing remission, bu...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/bjh.14475
更新日期:2017-04-01 00:00:00
abstract::Interferon(rIFN)-alpha, a successful therapeutic agent in the control of thrombocytosis, has been shown to suppress human megakaryopoiesis. We investigated bone marrow biopsies from 12 patients with thrombocytosis due to chronic myeloproliferative disorders. Prior to treatment as well as during rIFN-alpha-2c therapy, ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1990.tb02531.x
更新日期:1990-01-01 00:00:00
abstract::Platelet function was evaluated in eight patients with chronic granulocytic leukaemia (CGL), seven Ph1 positive and one Ph1 negative. Seven of the eight patients' platelets had an absence of the second wave of adrenaline induced aggregation on at least one occasion, while five had impaired collagen aggregation. The pl...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1978.tb05836.x
更新日期:1978-12-01 00:00:00
abstract::Multiple myeloma (MM) is a disease with known immune dysregulation. Natural killer (NK) cells have shown preclinical activity in MM. We conducted a first-in-human study of umbilical cord blood-derived (CB) NK cells for MM patients undergoing high dose chemotherapy and autologous haematopoietic stem cell transplantatio...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.14570
更新日期:2017-05-01 00:00:00
abstract::The effect of parenteral administration of IL-11 on gastrointestinal iron absorption was evaluated. A significant increase in the absorption of 59Fe-tagged food iron fed to fasting rats was observed when two subcutaneous injections of IL-11 were given 48 and 24 h prior to testing. Relatively similar increases of 25% w...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2141.1995.tb05275.x
更新日期:1995-09-01 00:00:00
abstract::Refractory anaemia with ring sideroblasts (RARS) is distinguished by hyperplastic inefficient erythropoiesis, aberrant mitochondrial ferritin accumulation and anaemia. Heterozygous mutations in the spliceosome gene SF3B1 are found in a majority of RARS cases. To explore the link between SF3B1 mutations and anaemia, we...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.13610
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abstract::Gaucher disease (GD) is an autosomal recessive inherited defect of the lysosomal enzyme glucocerebrosidase (GluCerase) that leads to glucosylceramide (GluCer) accumulation. We previously demonstrated the existence of imbalances in certain lymphocyte populations in GD patients. We now show that GluCerase-deficient mono...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2141.2005.05503.x
更新日期:2005-06-01 00:00:00
abstract::Among 750 previously untreated patients with multiple myeloma, 27 (4%) presented with plasma cell leukaemia. All but one patient had high tumour mass and, when compared with comparable patients without leukaemia, more frequent extraosseous involvement, thrombocytopenia, high serum lactate dehydrogenase and hypodiploid...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2141.1994.tb05114.x
更新日期:1994-12-01 00:00:00
abstract::Bone marrow angiogenesis is suggested to play a role in the pathogenesis of acute myeloid leukaemia (AML) and endothelial cells may mediate chemosensitivity. This study investigated in vitro endothelial effects of coculture of microvascular endothelial cells (MVEC) with AML cells derived from 33 consecutive AML patien...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2008.07411.x
更新日期:2009-01-01 00:00:00
abstract::With the aim of producing unique targets for malignant cells we have identified peptide ligands for the clonal surface immunoglobulin isolated from the B cells of a chronic lymphocytic leukaemia (CLL) patient. The peptides were identified from random-peptide phage-display libraries. The obtained ligands bound specific...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.0007-1048.2001.03311.x
更新日期:2002-03-01 00:00:00
abstract::Previously thought to be best described as a plasma cell disorder, Waldenström macroglobulinaemia (WM) is now understood to be a distinct clinicobiological entity. WM shares B-cell origin and certain other features with both chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM). WM and CLL arise from B-cells a...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2141.2007.06845.x
更新日期:2007-12-01 00:00:00
abstract::We report the clinical presentation and the morphological, immunophenotypic, cytogenetic and molecular genetic characteristics of a 14 1/2-year-old boy who had French-American-British (FAB) type M1 acute non-lymphocytic (ANLL) leukaemia with a common T-ALL immunological phenotype, with no myeloid associated antigen, e...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1994.tb03276.x
更新日期:1994-01-01 00:00:00
abstract::Primary long-term bone marrow cultures grown in 40 mM HEPES-buffered McCoy's 5A medium produced granulocyte-macrophage colony-forming units (CFU-GM) for a median of 9 weeks compared with 7 weeks with CO2/bicarbonate-buffered cultures. Reducing the medium glucose concentration (from 12.5 to 2.75 mM) extended the cultur...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.02002.x
更新日期:2000-06-01 00:00:00
abstract::Genome-wide association studies (GWAS) have shown that the 8q24 region harbours multiple independent cancer susceptibility loci, even though it is devoid of genes. Given that no GWAS data are currently available for multiple myeloma (MM), we tested the hypothesis that genetic variants in this region could play a role ...
journal_title:British journal of haematology
pub_type: 杂志文章,meta分析
doi:10.1111/j.1365-2141.2012.09047.x
更新日期:2012-05-01 00:00:00
abstract::The glycoprotein localization of the platelet-specific antigens Zwa, Zwb and Baka and their presence on tryptic fragments of glycoproteins was studied by immunoblotting. Human platelets were solubilized and pre-cleared from platelet-associated IgG. The glycoproteins were separated on SDS polyacrylamide gels, transferr...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1986.tb02233.x
更新日期:1986-12-01 00:00:00
abstract::AML1/RUNX1, which encodes a transcription factor essential for definitive haematopoiesis, is a frequent target of leukaemia-associated chromosome translocations. Point mutations of this gene have also recently been associated with leukaemia and myelodysplastic syndrome (MDS). To further define the frequency and biolog...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2004.04966.x
更新日期:2004-06-01 00:00:00
abstract::We evaluated the blood from 150 patients with primary AL-amyloidosis for circulating monoclonal plasma cells using a sensitive slide-based immunofluorescence technique. The percentage of monoclonal blood plasma cells (BPC) that were in S-phase was determined by the bromodeoxyuridine labelling index (BLI). Monoclonal B...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.00583.x
更新日期:1998-02-01 00:00:00
abstract::In this study we have carried out haplotype analysis at the beta-globin gene cluster and defined the beta-thalassaemia mutations in a large Sardinian family, ascertained through a proband with thalassaemia major, in which several members were carriers of a beta-thalassaemia allele characterized by microcytosis, hypoch...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1987.tb02331.x
更新日期:1987-10-01 00:00:00
abstract::We have previously shown that allogeneic bone marrow transplantation (BMT) with cryopreserved donor marrow cells can be used without prolonging the engraftment time or interfering with the reconstitution of haemopoiesis. In this report we extend our initial observations of the first 40 patients who underwent allogenei...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1997.d01-2032.x
更新日期:1997-02-01 00:00:00
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journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.02214.x
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journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1980.tb08718.x
更新日期:1980-04-01 00:00:00
abstract::The combined incidence of classical Philadelphia-negative myeloproliferative neoplasm (MPN) is 6-9/100 000 with a peak frequency between 50 and 70 years. MPN is less frequent in women of reproductive age. However, for essential thrombocythaemia (ET) in particular there is a second peak in women of reproductive age and...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/bjh.16453
更新日期:2020-05-01 00:00:00
abstract::A bleeding tendency manifested by petechiae and ecchymoses is one of the most common causes for referral of patients to haematology clinics. Vessel wall pathology is not usually considered to be a cause for deranged haemostasis, although coexistence of increased capillary fragility and joint hypermobility have been re...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.00697.x
更新日期:1998-05-01 00:00:00
abstract::A serial study of coagulation activation and whole-blood viscosity was performed on 37 patients with local or systemic bacterial infection, malaria, or a viral infection. Thrombocytopenia, without consumption of coagulation factors, was the main feature of benign tertian malaria and viral infection, whereas in septica...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1979.tb01155.x
更新日期:1979-07-01 00:00:00
abstract::Patients with multiple myeloma (MM) undergoing high dose therapy and autologous stem cell transplantation (SCT) remain at risk for disease progression. Induction of the expression of highly immunogenic cancer testis antigens (CTA) in malignant plasma cells in MM patients may trigger a protective immune response follow...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2012.09225.x
更新日期:2012-09-01 00:00:00
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,...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/bjh.12691
更新日期:2014-02-01 00:00:00
abstract::The expression of three onc-genes, c-myc, c-myb and c-fes, has been evaluated at the cellular level in myeloid and erythroid precursors of normal human bone marrow, by "in situ" hybridization with tritium-labelled probes. A relatively large amount of m-RNA from the three onc-genes was detected in myeloblasts and promy...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1986.tb02931.x
更新日期:1986-02-01 00:00:00
abstract::Increasing demand for population screening for the haemoglobinopathies gives rise to a requirement for high throughput systems, which allow for cost effective, rapid, sensitive and specific screening of clinically significant haemoglobins. We have developed a practical and efficient approach using tryptic digestion an...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2005.05646.x
更新日期:2005-08-01 00:00:00
abstract::Although the combination of tyrosine kinase inhibitors with chemotherapy is widely used for young adults with Philadelphia chromosome positive-acute lymphoblastic leukaemia (Ph+ ALL), the outcome and safety of this combination using intensive paediatric-based protocols has not been well described. The clinical course ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2012.09182.x
更新日期:2012-08-01 00:00:00
abstract::This study investigates the value of performing a staging bone marrow in patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and classical hodgkin lymphoma (CHL). The results of 3112 staging bone marrow examinations were assessed for impact on prognostic assessment and critical treatment deci...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.13412
更新日期:2015-07-01 00:00:00