Abstract:
:Over the past four decades, remarkable progress has been made in the treatment and prognosis of multiple myeloma (MM), although it remains an incurable disease. Chemotherapy resistance is a major hurdle for treatment efficacy. Drug resistance can be innate and so driven by genes involved in the drug metabolism pathways. We performed an association study of 71 germline variants within the major genes in those pathways (ABCB1, ABCC2, ABCG2, and their regulators NR1I2/PXR and NR1I3/CAR) in the International Multiple Myeloma rESEarch (IMMEnSE) consortium, consisting of 1365 MM cases with survival information recruited in 5 European countries. Two of the SNPs showed a significant association with the survival of MM patients, namely rs2235013, located in ABCB1 [Hazard ratio (HR) = 1·52, 95% confidence interval (CI) = 1·18-1·95, P = 0·00087], and rs4148388, located in ABCC2 (HR = 2·15, 95% CI = 1·44-3·22, P = 0·0001). ABCC2 plays an essential role in transporting various anticancer drugs, including several used against MM, out of the cell. In silico analyses predict that the variant alleles of four SNPs in linkage disequilibrium with ABCC2-rs4148388 are associated with increased gene expression. Overexpression of ABCC2 increases drug clearance and therefore may induce drug resistance mechanisms. In conclusion, we found a promising association between ABCC2-rs4148388 and MM outcome that is supported by a plausible biological explanation.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Macauda A,Castelli E,Buda G,Pelosini M,Butrym A,Watek M,Kruszewski M,Vangsted AJ,Rymko M,Jamroziak K,Abildgaard N,Haastrup EK,Mazur G,Ríos R,Jurczyszyn A,Zawirska D,Dudziński M,Raźny M,Dutka M,Tomczak W,Suska A,doi
10.1111/bjh.15521subject
Has Abstractpub_date
2018-11-01 00:00:00pages
375-384issue
3eissn
0007-1048issn
1365-2141journal_volume
183pub_type
临床试验,杂志文章,多中心研究abstract::We investigated the origin of bone marrow fibroblasts in three bone marrow transplant recipients with aplastic anaemia and leukaemia who received grafts from HLA-identical siblings of opposite sex. The patients were conditioned for transplantation with high doses of cytotoxic drugs and 300--1000 rads total body irradi...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1980.tb01200.x
更新日期:1980-02-01 00:00:00
abstract::Patients belonging to four families with 'atypical elliptocytosis' have been investigated. Clinical, haematological, erythrokinetic and enzymatic characteristics as well as the effect of splenectomy are discussed. These studies appear to define the fundamental features of a particular disorder or a variety of heredita...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1979.tb03770.x
更新日期:1979-11-01 00:00:00
abstract::Fetal haemoglobin levels have been measured prospectively in 135 autopsy cases of sudden, unexpected infant deaths (31 pre-term, 104 full term) using standard laboratory methods. These results have been compared with Hb F values from a normal control group of 570 living infants (145 pre-term, 425 full-term) with a pos...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1992.tb06440.x
更新日期:1992-10-01 00:00:00
abstract::The aim of this study was to evaluate the role of markers of bone remodelling, and osteoclast activation/function in patients with monoclonal gammopathy of undetermined significance (MGUS). We have measured serum levels of soluble RANKL (sRANKL), osteoprotegerin (OPG), macrophage inflammatory protein-1alpha (MIP-1alph...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2004.05092.x
更新日期:2004-09-01 00:00:00
abstract::The endothelial hybridoma (EAhy926) cell line was employed to clarify whether antiphospholipid antibodies (aPA) [lupus anticoagulant (LA), antiprothrombin antibody (aPT) and/or anticardiolipin antibody (aCL)] and anti-endothelial cell antibodies (AECA) are identical, and establish whether beta2-glycoprotein I (beta2-G...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1997.d01-2147.x
更新日期:1997-04-01 00:00:00
abstract::A prospective study of 7065 consecutive new pregnancies identified 230 with a positive screen, of which 27% (62/230) were 'enzyme-only' antibodies. 32 of these (52%) were potentially clinically important and were all of Rh specificity: 22 anti-E, seven anti-Cw, two anti-D and one anti-c. However, only three of these e...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1999.01618.x
更新日期:1999-09-01 00:00:00
abstract::Lenalidomide (LEN) acts directly on multiple myeloma (MM) cells by inducing cereblon-mediated degradation of interferon regulatory factor 4, Ikaros (IKZF)1 and IKZF3, transcription factors that are essential for MM cell survival. The mucin 1 (MUC1) C-terminal transmembrane subunit (MUC1-C) oncoprotein is aberrantly ex...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.14801
更新日期:2017-09-01 00:00:00
abstract::Although the expression patterns of the members of the tumour necrosis factor receptor and ligand families have extensively been studied by flow-cytometry on stimulated peripheral blood mononuclear cells (PBMNC), little or no flow-cytometric or immunohistological data exist about their expression in lymphoid tissue. A...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1997.3153134.x
更新日期:1997-09-01 00:00:00
abstract::The erythrocyte chemokine receptor, a receptor for Plasmodium vivax, carries the antigens of the Duffy blood group system. Sequence analysis of reticulocyte RNA from individuals of known Duffy phenotype showed that the Fya antigen differs from the Fyb antigen as a result of a single nucleotide difference (A131 or G) e...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1995.tb05202.x
更新日期:1995-08-01 00:00:00
abstract::Heparin binding on polymorphonuclear leucocytes (PMNL) was characterized. Heparin binding was specific, rapid, saturable and reversible. One single class of heparin binding sites was found with a dissociation constant of 1.22 mumol/l and 7.7 x 10(6) sites per PMNL. The binding was independent of the anticoagulant acti...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1992.tb08176.x
更新日期:1992-05-01 00:00:00
abstract::We performed a retrospective study analysing the effect of sorafenib, an oral fms-Like Tyrosine Kinase 3 (FLT3)/multikinase inhibitor, as post-transplant maintenance in adult patients with FLT3-internal tandem duplication (ITD) acute myeloid leukaemia (AML). We identified consecutive patients with FLT3-ITD AML diagnos...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.14260
更新日期:2016-11-01 00:00:00
abstract::Peripheral blood mononuclear cells (PBMNC) from 23 healthy subjects and 39 patients with B-cell chronic leukaemia (B-CLL) were assayed for ribonuclease H activity using as substrate the filter-immobilized synthetic homopolymer hybrid 3H-poly(rA):poly(dT). In 69% of the leukaemia patients examined enzyme activities wer...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1988.tb02486.x
更新日期:1988-11-01 00:00:00
abstract::Unfractionated heparin (UFH) and low-molecular weight heparin (LMWH) are well defined anticoagulant agents. Recent data suggest that both LMWH and UFH may also have potent anti-inflammatory properties; however, their mechanism of action responsible for the anti-inflammatory effect is not yet fully elucidated. This stu...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2006.05959.x
更新日期:2006-04-01 00:00:00
abstract::Most haemolytic disease is mediated by immunoglobulin G (IgG) antibodies and leads to red blood cell destruction outside of the circulatory system. However, rare syndromes, such as paroxysmal cold haemoglobinuria, show IgG antibodies causing intravascular destruction. Haemolysis may also occur because of immunoglobuli...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2141.2007.06664.x
更新日期:2007-08-01 00:00:00
abstract::The spleen acts as a blood filter and lymphopoietic organ. Asplenic and hyposplenic individuals are more susceptible to serious infections caused by encapsulated bacteria but they can be protected by antibiotic prophylaxis and immunizations. Recent progress in vaccinology means prophylaxis is now successful in the vas...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/bjh.13660
更新日期:2015-12-01 00:00:00
abstract::Erythrocytes from elderly donors (> 70 years), but not young donors (18-35 years), are shown to undergo sequestration in an in vitro erythrophagocytosis assay. Comparable levels of sequestration are observed for high density erythrocytes from young individuals and both low density and high density erythrocytes from el...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1993.tb04705.x
更新日期:1993-04-01 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::Marked changes in the concentration and proliferative state of circulating granulocytic progenitor cells (colony forming units in culture; CFUc) were observed in female patients following surgical trauma. Within one day of an abdominal hysterectomy there was an abrupt fall in the number of blood CFUc to between 10% an...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1980.tb01208.x
更新日期:1980-02-01 00:00:00
abstract::Besides circulating in normal plasma, von Willebrand factor (VWF) is also stored at relatively high concentration within the alpha-granules of platelets. This pool of platelet VWF exists distinct from plasma VWF, and is enriched in haemostatically-active high molecular weight multimers. Interestingly, the glycosylatio...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2141.2009.08052.x
更新日期:2010-03-01 00:00:00
abstract::Many immune dysfunctions participate in immune thrombocytopenia (ITP) pathogenesis, including numeric and functional defects in suppressor T (Ts) cells and immune-regulation abnormalities in mesenchymal stem cells (MSCs). Recent studies showed that MSCs can promote Ts cell differentiation. Thus, we compared the Ts cel...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.16953
更新日期:2020-07-16 00:00:00
abstract::Evidence regarding the efficacy of gemtuzumab ozogamicin (GO) addition to standard induction chemotherapy in newly diagnosed acute myeloid leukaemia (AML) is conflicting. This systematic review aimed to identify and summarize all evidence regarding the benefits and harms of adding GO to conventional chemotherapy for i...
journal_title:British journal of haematology
pub_type: 杂志文章,meta分析,评审
doi:10.1111/bjh.12528
更新日期:2013-11-01 00:00:00
abstract::To assess and define the effects of heterocellular hereditary persistence of fetal haemoglobin (HPFH) on the haematological phenotype of heterozygous beta-thalassaemia, we have studied a large kindred that included a total of 204 subjects with 60 beta-thalassaemia carriers, of whom 35 were also heterozygous, and five ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2003.04600.x
更新日期:2003-10-01 00:00:00
abstract::Budd-Chiari syndrome and portal vein thrombosis (BCS/PVT) are frequently associated with polycythaemia vera (PV). In an attempt to elucidate the mechanisms of BCS/PVT secondary to PV (T-PV), CD11b neutrophil expression, neutrophil oxidative burst and platelet-neutrophil complexes (PNC) were assessed in 17 such patient...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2003.04770.x
更新日期:2004-02-01 00:00:00
abstract::The specific sodium pump antagonist ouabain was used to study the effect of sodium pump inhibition on granulopoietic colony formation by normal human bone marrow cells cultured in soft agar for 7 d. Suppression of colony formation was dose-dependent and occurred at a low and reproducible concentration. The use of an e...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1982.tb02795.x
更新日期:1982-07-01 00:00:00
abstract::We have evaluated the function of granulocytes in 14 patients suffering from myelodysplastic syndrome (MDS). We also evaluated the functional and immunochemical activities of five monoclonal antibodies (MoAbs) reactive with the CD11/CD18 leucocyte adhesion molecules of granulocytes. Granulocytes showed a decrease in c...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1993.tb08279.x
更新日期:1993-02-01 00:00:00
abstract::Three male patients (two of whom were brothers) with Shwachman-Diamond (SDS) syndrome presented with acute myeloid leukaemia in adulthood. In all three cases there was trilineage myelodysplasia and the morphology was consistent with FAB subtype M6. SDS is an inherited bone marrow failure syndrome with a high propensit...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1997.3673181.x
更新日期:1997-10-01 00:00:00
abstract::We explored the prognostic factors for children with very high-risk (VHR) Philadelphia chromosome (Ph) negative B-cell acute lymphoblastic leukaemia (B-ALL) and compared the therapeutic effects of intensive chemotherapy and unmanipulated haploidentical haematopoietic stem cell transplantation (haplo-HSCT) as post-remi...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/bjh.16226
更新日期:2020-03-01 00:00:00
abstract::We evaluated the performance of eight d-assays for the exclusion of deep vein thrombosis (DVT); Biopool AutoDimer, Biopool MiniQuant, bioMèrieux MDA D-Dimer, VIDAS, Dade Behring D-Dimer Plus, Trinity Biotech AMAX, NycoCard D-dimer and IL Test D-Dimer. The assays were evaluated both as stand-alone tests, and in combina...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2005.05394.x
更新日期:2005-03-01 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::This retrospective study aimed to analyse the impact on overall survival (OS) and event-free survival (EFS) of chimaerism status and kinetics following allogeneic conventional and reduced-intensity conditioning haematopoietic stem cell transplantation, and to compare this with the impact of other well-known factors. W...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2005.05372.x
更新日期:2005-03-01 00:00:00