Abstract:
:It has been shown that granulocyte/macrophage colony stimulating factor (GM-CSF) is able to support myeloma cell propagation in cooperation with interleukin (IL)-6, the major growth factor for malignant plasma cells, although the biological mechanisms involved remain unknown. Therefore we investigated (i) the expression levels of the GM-CSF receptor (GM-CSFR) constituents in three malignant plasma cell lines and in native malignant plasma cells, (ii) the ability of the receptor to mediate common signalling pathways regulating proliferation and cell survival in malignant plasma cell lines, and (iii) the effects of GM-CSF on tumour cell biology. The GM-CSFRalpha subunit was detected in the malignant plasma cell lines RPMI-8226, MC/CAR, IM-9 as well as 6/6 native myeloma cell samples derived from the bone marrow of patients with overt disease. Furthermore, GM-CSFR expression was also detected in the CD19+ fraction from 2/3 bone marrow samples and 5/8 peripheral blood samples derived from patients with malignant plasma cell disorders, but not in the CD19+ fraction of peripheral blood from healthy donors. The expressed cytokine receptor alpha-subunit was able to constitute a functional signalling complex with the ubiquitously expressed GM-CSFRbeta subunit, as demonstrated by the fact that GM-CSF induced the p21-ras/mitogen-activated protein kinase (MAPK) signalling cascade in malignant plasma cell lines. Since this signalling cascade plays an essential role in the mediation of both proliferation and cell survival, we investigated the impact of GM-CSF on these two events. Application of GM-CSF led to an increase of DNA-synthesis in MC/CAR, IM-9 and RPMI-8226 cells. Furthermore, it increased longevity of these malignant plasma cell lines by reducing the rates of spontaneous apoptosis. We conclude that (i) the functional GM-CSFR is commonly expressed on malignant plasma cells and that (ii) GM-CSF promotes the clonal expansion of myeloma cells by inhibiting spontaneous apoptosis and promoting DNA synthesis.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Villunger A,Egle A,Kos M,Egle D,Tinhofer I,Henn T,Uberall F,Maly K,Greil Rdoi
10.1046/j.1365-2141.1998.00880.xsubject
Has Abstractpub_date
1998-09-01 00:00:00pages
1069-80issue
4eissn
0007-1048issn
1365-2141journal_volume
102pub_type
杂志文章abstract::A number of studies have demonstrated induction of the unfolded protein response (UPR) in patients with severe congenital neutropenia (CN) harbouring mutations of ELANE, encoding neutrophil elastase. Why UPR is not activated in patients with cyclic neutropenia (CyN) carrying the same ELANE mutations is unclear. We eva...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.13823
更新日期:2016-01-01 00:00:00
abstract::The clinical significance of Aspergillus fungaemia in the setting of a deep-seated aspergillosis has not been clearly established. Among 107 microbiologically documented Aspergillus infections in patients with haematological diseases observed over a 17-year period, blood cultures grew Aspergillus species from 10 cases...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2141.2001.02901.x
更新日期:2001-07-01 00:00:00
abstract::Prospective studies in children with B-precursor acute lymphoblastic leukaemia (ALL) have shown that polymerase chain reaction (PCR)-based detection of minimal residual disease (MRD) using immunoglobin (Ig) and T-cell receptor (TCR) gene rearrangements as targets can be used to identify patients with a high relapse ri...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03228.x
更新日期:2002-01-01 00:00:00
abstract::In vitro colony formation of bone-marrow erythroid progenitor cells in patients with paroxysmal nocturnal haemoglobinuria (PNH) was examined. The numbers of early and late erythroid progenitors (BFU-E and CFU-E) showed wide variations; two cases out of eight cases of PNH showed decreased erythroid colony formation, bu...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1982.tb01919.x
更新日期:1982-02-01 00:00:00
abstract::In a patient with immune thrombocytopenic purpura (ITP), we found a novel platelet-activating IgG (act-IgG) and an inhibitory IgG (inhi-IgG) that prevented activation induced by both CD9 monoclonal antibody (mAb) and the act-IgG. Purified IgG from the patient plasma caused a rise in [Ca2+]i and the aggregation of norm...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1993.tb03148.x
更新日期:1993-08-01 00:00:00
abstract::Karyotypic analysis was performed in a total of 69 patients with well-characterized idiopathic myelofibrosis. Karyotypic abnormalities were detected in 46% of cases examined during the chronic phase (29/63); with three abnormalities, del(13q), del(20q) and partial trisomy 1q, accounting for 75% of all abnormalities at...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1994.tb05076.x
更新日期:1994-11-01 00:00:00
abstract::Kinetic studies were performed to determine the clearance of iodinated transferrin in hypotransferrinaemic mice, as compared to normal animals. Clearance of i.v. (and i.p.) administered radiolabelled protein in homozygous (hpx/hpx) mice was significantly faster than in heterozygous (hpx/+) and wild-type control (+/+) ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1995.tb08926.x
更新日期:1995-01-01 00:00:00
abstract::Mutations in SOCS1 are frequent in primary mediastinal B-cell lymphoma and classical Hodgkin lymphoma. In the latter, SOCS1 mutations affect the length of the encoded protein (major mutations) and are associated with shorter patient survival. Two independent studies examined the prognostic impact of SOCS1 mutations in...
journal_title:British journal of haematology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bjh.16147
更新日期:2019-12-01 00:00:00
abstract::Following bone marrow stem cell transplantation allo-responses against haemopoietic progenitor cells (HPC), causing graft rejection and graft-versus-leukaemia effects, can be induced by donor T cells recognizing peptides derived from polymorphic endogenous proteins present in HPC. Since CD33 and CD34 are both expresse...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.00906.x
更新日期:1998-09-01 00:00:00
abstract::The Fanconi anaemia protein FANCD2 suppresses PPARƔ to maintain haematopoietic stem cell's (HSC) function; however, the underlying mechanism is not known. Here we show that FANCD2 acts in concert with the Notch target HES1 to suppress inflammation-induced PPARƔ in HSC maintenance. Loss of HES1 exacerbates FANCD2-KO HS...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.17230
更新日期:2020-11-22 00:00:00
abstract::Pulmonary hypertension (PH) can complicate myelofibrosis with myeloid metaplasia (MMM), may arise in the absence of evidence for thromboembolic disease and carries a grim prognosis. Four patients with MMM and severe symptomatic PH were treated with whole-lung external beam radiotherapy in a single fraction of 100 cGy....
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03695.x
更新日期:2002-09-01 00:00:00
abstract::In this paper we describe the placental transport of [3H]vitamin K1 in pregnant rats during the first 24 h after the oral administration of the vitamin. Vitamin K1 in the fetal livers ranged from 0.13% (3 h) to 2% (24 h) of the values found in the corresponding maternal livers. In spite of the low placental transfer o...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1987.tb06863.x
更新日期:1987-03-01 00:00:00
abstract::Diamond-Blackfan anaemia (DBA) is a constitutional pure red cell aplasia presenting in early childhood. In some patients, neutropenia and/or thrombocytopenia have also been observed during the course of the disease. We have followed 28 patients with steroid-refractory DBA for up to 13 years with serial peripheral bloo...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.01796.x
更新日期:2000-01-01 00:00:00
abstract::In two unrelated Spanish males with glucose-6-phosphate dehydrogenase (G6PD) deficiency and haemolytic anaemia, and two different novel point mutations in the G6PD gene, have been identified. A C to T transition at nucleotide 406 resulting in a (136) Arg to Cys substitution and a C to G transition at nucleotide 1155 r...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1997.2563071.x
更新日期:1997-09-01 00:00:00
abstract::The in vitro growth characteristics of a large series of acute myeloid leukaemia (AML) patients and their relationship with other clinical and biological disease characteristics were analysed. Patients with AML were studied, 181 with de novo AML and 45 with secondary AML (24 myelodysplastic syndrome, sAML-MDS, 21 myel...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.00962.x
更新日期:1998-10-01 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::In this population-based survey covering two geographically distinct UK regions, we evaluated the number of myeloma patients aged < or =65 years who have not undergone transplantation. The combined data from both of these regions showed that 57% of age-eligible patients were not transplanted. While early death and com...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2004.05340.x
更新日期:2005-02-01 00:00:00
abstract::Membrane protein synthesis in human immature erythroid cells was studied by incubating the cells with 35S-methionine in vitro. The radioactive precursor amino acid was incorporated into membrane protein in a linear fashion for approximately 60 min, after which there was only a slight increase in incorporation. Intrace...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1981.tb02777.x
更新日期:1981-02-01 00:00:00
abstract::Chronic immune thrombocytopenia (ITP) is a haematological disorder in which patients predominantly develop skin and mucosal bleeding. Early studies suggested ITP was primarily due to immune-mediated peripheral platelet destruction. However, increasing evidence indicates that an additional component of this disorder is...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2141.2009.07717.x
更新日期:2009-09-01 00:00:00
abstract::Overt ischaemic stroke is one of the most devastating complications in children with sickle cell disease (SCD). The compensatory response to anaemia in SCD includes an increase in cerebral blood flow (CBF) by accessing cerebrovascular dilatory reserve. Exhaustion of dilatory reserve secondary to anaemic stress may lea...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.14424
更新日期:2017-01-01 00:00:00
abstract::Human bone marrow mesenchymal stem cells (MSC) generate, via a fibroblast colony-forming unit (CFU-F), osteo-chondroblastic cells as well as adipocytes and stromacytes. To date, these stem cells are isolated indirectly using a cell culture method and phenotyped as CD45 negative while the in vivo counterparts are undet...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2003.04469.x
更新日期:2003-08-01 00:00:00
abstract::18F-fluoro-deoxyglucose (FDG) positron emission tomography (PET) might be a better tool than computerized tomography (CT) in predicting long-term treatment outcome in patients with relapsed chemosensitive lymphoma who are candidates for autologous stem cell transplantation (ASCT). We studied patients with recurrent or...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2003.04593.x
更新日期:2003-10-01 00:00:00
abstract::Protein S is expressed in a number of tissue types, one of the most physiologically relevant being the liver. However, transcriptional control of protein S gene expression is poorly understood. We have characterised a 638 bp area in the 5' flanking region of the human protein S gene, spanning all 10 previously reporte...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2006.06327.x
更新日期:2006-11-01 00:00:00
abstract::The variable clinical outcomes of Multiple Myeloma (MM) patients are incompletely defined by current prognostication tools. We examined the clinical utility of high-resolution telomere length analysis as a prognostic marker in MM. Cohort stratification, using a previously determined length threshold for telomere dysfu...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.14643
更新日期:2017-07-01 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
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::Lack of consensus for first-line marginal zone lymphoma (MZL) treatment and toxicities associated with currently available systemic therapies have inspired evaluation of immunotherapeutic agents yielding robust outcomes with improved tolerability. We previously reported durable efficacy with first-line lenalidomide an...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.15843
更新日期:2019-06-01 00:00:00
abstract::Endothelial progenitor cells (EPCs) were recently demonstrated to exist in human cord blood. Phytohaemagglutinin (PHA), a potent mitogen for mononuclear cells was used to induce EPCs from unsorted cord blood mononuclear cells (CBMCs). Adherent cells in clusters appeared approximately 24 h after CBMCs were cultured in ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2001.02694.x
更新日期:2001-06-01 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::Pituitary tumour transforming gene (PTTG) isolated from pituitary tumour cells transforms cells in vitro and causes in vivo tumour formation. PTTG is expressed in several human tumours and cell lines. In normal adult tissues, the testis expresses abundant levels of PTTG mRNA comparable to that found in tumour cells. A...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03941.x
更新日期:2002-12-01 00:00:00