Abstract:
:The replicative potential of human CD56(+) CD3(-) natural killer (NK) cells is unknown. We found that by exposing NK cells to the leukaemic cell line K562 genetically modified to express 4-1BB ligand and interleukin 15 (K562-mb15-41BBL), they expanded for up to 30 population doublings, achieving numbers that ranged from 1.6 x 10(5) to 1.2 x 10(11)% (median, 5.9 x 10(6)%; n = 7) of those originally seeded. However, NK cells eventually became unresponsive to stimulation and died. Their demise could be suppressed by enforcing the expression of the human telomerase reverse transcriptase gene (TERT). TERT-overexpressing NK cells continued to proliferate in response to K562-mb15-41BBL stimulation for more than 1 year of culture, while maintaining a normal karyotype and genotype. Long-lived NK cells had high cytotoxicity against myeloid and T-lineage leukaemic cells. They remained susceptible to genetic manipulation, becoming highly cytotoxic to B-lineage leukaemic cells after expression of anti-CD19 signaling receptors. Thus, human NK cells have a replicative potential similar to that of T lymphocytes and their lifespan can be significantly prolonged by an increase in TERT activity. We suggest that the methods described here should have many applications in studies of NK cell biology and NK cell-based therapies.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Fujisaki H,Kakuda H,Imai C,Mullighan CG,Campana Ddoi
10.1111/j.1365-2141.2009.07667.xsubject
Has Abstractpub_date
2009-06-01 00:00:00pages
606-13issue
5eissn
0007-1048issn
1365-2141pii
BJH7667journal_volume
145pub_type
杂志文章abstract::A patient with Jo-1 antibody-associated polymyositis (Jo-1 PM) had a Karnofsky score of 40% and severe muscle, liver and lung damage that was refractory to standard therapy. The female patient received an autologous T-cell-depleted haematopoietic stem cell transplant (HSCT) after myeloablative conditioning. The transp...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.02191.x
更新日期:2000-08-01 00:00:00
abstract::Plasma iron turnover (PIT) and ferritin synthesis in the liver and spleen were studied in rats within the first 24 h of inflammation produced by turpentine injection. Comparison of the sequential changes in PIT and ferritin synthesis showed that alterations in ferritin synthesis preceded the changes in plasma iron exc...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:
更新日期:1977-09-01 00:00:00
abstract::Sickle cell anaemia is a severe inherited blood disorder for which there is presently no curative therapy other than allogeneic haematopoietic stem cell (HSC) transplantation. This therapeutic option, however, is not available to most patients because of the lack of a matched related donor. Different genetic strategie...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2141.2011.08773.x
更新日期:2011-09-01 00:00:00
abstract::Sickle cell disease (SCD) is complicated by silent cerebral infarcts, visible as white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI). Both local vaso-occlusion, elicited by endothelial dysfunction, and insufficiency of cerebral blood flow (CBF) have been proposed to be involved in the aetiology. W...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.13819
更新日期:2016-01-01 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::High-dose dexamethasone (HD-Dex) has been reported to benefit AL amyloidosis patients with varying response rates. Our preliminary experience with the usual HD-Dex schedule indicated that the induction phase was rather toxic in AL patients. We therefore adopted a milder schedule consisting of dexamethasone 40 mg on d ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2001.02859.x
更新日期:2001-06-01 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::Impaired switching from fetal haemoglobin (HbF) to adult globin gene expression leads to hereditary persistence of fetal haemoglobin (HPFH) in adult life. This is of prime interest because elevated HbF levels ameliorate β-thalassaemia and sickle cell anaemia. Fetal haemoglobin levels are regulated by complex mechanism...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2010.08303.x
更新日期:2010-09-01 00:00:00
abstract::Platelets in an infant with Chediak-Higashi (C-H) syndrome without bleeding manifestations and not in the accelerated phase showed abnormal function consistent with storage pool disorder as shown by abnormal aggregation, decreased storage capacity and release of [14C]5-HT, low endogenous 5-HT, reduced ATP and ADP with...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1977.tb00618.x
更新日期:1977-04-01 00:00:00
abstract::Adults with acute leukaemia and abnormalities of chromosome 11q23 have a poor prognosis when treated with conventional chemotherapy. To determine whether more intensive therapy can improve outcome for patients with this karyotypic finding, a retrospective analysis of all patients with acute leukaemia and 11q23 abnorma...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.01030.x
更新日期:1998-12-01 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::Cytotoxic T lymphocyte (CTL) lines specific for allogeneic antigens were generated by in vitro stimulation of donor-derived peripheral blood mononuclear cells obtained from patients who received human leucocyte antigen (HLA)-matched allogeneic haematopoietic stem cell transplantation (HSCT). One of the allogeneic anti...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2005.05843.x
更新日期:2006-01-01 00:00:00
abstract::During the administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) or granulocyte-macrophage CSF (rhGM-CSF) we studied the early and late changes of membrane antigen density on neutrophils. RhG-CSF and rhGM-CSF both caused an early transient reduction in blood neutrophilic granulocyte-conce...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1993.tb08644.x
更新日期:1993-09-01 00:00:00
abstract::Analogous to T cells, Natural Killer (NK) cells may facilitate engraftment, combat infection, and control cancer in bone marrow or haematopoietic stem cell transplantation (HSCT); however, NK cells do not cause graft-versus-host disease. Killer immunoglobulin-like receptors (KIRs) regulate NK cell function, and recent...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2141.2011.08823.x
更新日期:2011-10-01 00:00:00
abstract::Chronic graft-versus-host disease (cGVHD) is a common complication following allogeneic haematopoietic cell transplantation (HCT). It is the leading cause of non-relapse mortality in transplant survivors and has a significant impact upon their functional status and quality of life. Despite significant advances being m...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2141.2007.06652.x
更新日期:2007-07-01 00:00:00
abstract::Twenty-six members of four generations of one family in which a man was diagnosed in 1961 as having von Willebrand's disease (vWD) have been studied. Subtype IIB vWD and autosomal dominant inheritance was identified in 19 individuals with bleeding signs varying in severity and frequency. The absence of high molecular ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1988.tb02406.x
更新日期:1988-08-01 00:00:00
abstract::In whole blood from splenectomized subjects (n = 20), red cells showed a significant increase of mean surface area (MSA), mean cell volume (MCV), MSA/MCV-ratio and osmotic resistance, with the mean cell haemoglobin concentration (MCHC) being decreased. Studies on red cell populations of different cell age revealed tha...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1988.tb07605.x
更新日期:1988-05-01 00:00:00
abstract::We report a Lancashire family with mild haemophilia B associated with a -6 G to A mutation in the factor IX promoter. This mutation has been reported previously in Britain in one other affected family. The factor IX haplotype of these two unrelated patients was determined by PCR analysis of seven polymorphic sites wit...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1993.tb08667.x
更新日期:1993-09-01 00:00:00
abstract::Langerhans cell histiocytosis (LCH), the most common histiocytic disorder, is characterized by the accumulation of CD1A(+) /CD207(+) mononuclear phagocytes within granulomatous lesions that can affect nearly all organ systems. Historically, LCH has been presumed to arise from transformed or pathologically activated ep...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/bjh.13247
更新日期:2015-04-01 00:00:00
abstract::In myeloid malignancies, T-cell and NK function has been shown to deteriorate with transformation from pre-leukaemia to advanced disease. Immune dysfunction in solid tumours has been attributed to abnormal signal transduction, possibly through altered expression of intracellular components of the TCR/CD3 complex (e.g....
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.00654.x
更新日期:1998-03-01 00:00:00
abstract::Sézary syndrome and Mycosis fungoides are the most common forms of cutaneous T-cell lymphomas. To assess the response to different therapies especially in Sézary syndrome, it is helpful to monitor the percentage of circulating tumour cells in the blood. The use of T-cell receptor (TCR)-Vbeta specific monoclonal antibo...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03726.x
更新日期:2002-09-01 00:00:00
abstract::Virchow's triad describes three factors that contribute to the development of venous thrombosis: hypercoagulability, stasis and endothelial injury. Yet, extensive review of the historical literature casts doubt on the existence of a triad described by Virchow in the form it is currently quoted throughout contemporary ...
journal_title:British journal of haematology
pub_type: 传,历史文章,杂志文章
doi:10.1111/j.1365-2141.2008.07323.x
更新日期:2008-10-01 00:00:00
abstract::We report three cases of platelet dysfunction characterized by defective Ca2+ ionophore-induced platelet aggregation without impaired production of thromboxane A2 (TXA2). The patients had mild to moderate bleeding tendencies, and their platelet aggregation and secretion induced by ADP, collagen, arachidonic acid, stab...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2001.02637.x
更新日期:2001-03-01 00:00:00
abstract::Guidelines on hereditary spherocytosis (HS) published in 2004 (Bolton-Maggs et al, 2004) are here replaced to reflect changes in current opinion on the surgical management, (particularly the indications for concomitant splenectomy with cholecystectomy in children with mild HS, and concomitant cholecystectomy with sple...
journal_title:British journal of haematology
pub_type: 杂志文章,实务指引
doi:10.1111/j.1365-2141.2011.08921.x
更新日期:2012-01-01 00:00:00
abstract::Two patients with acute immune haemolytic anaemia caused by diclofenac are described. Both patients had developed IgG drug-independent autoantibodies and drug-dependent antibodies. The drug-dependent antibodies in one patient reacted with red blood cells (RBC) only in the presence of urine from patients receiving dicl...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1991.tb08624.x
更新日期:1991-04-01 00:00:00
abstract::Epstein-Barr virus-associated haemophagocytic lymphohistiocytosis (EBV-HLH) is one of the most common subtypes of secondary HLH. However, more than 30% of patients do not respond to traditional treatment. Here, we investigated the efficacy and safety of the L-DEP regimen as a salvage therapy for paediatric refractory ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.16861
更新日期:2020-11-01 00:00:00
abstract:SUMMARY:We report two patients with chronic myeloid leukaemia (CML) developing hypoplasia and karyotype conversion after conventional busulphan therapy. Initially, the percentage of Ph-positive metaphases in marrow for both patients was 100%, which steadily diminished up to a complete disappearance in case 1 and decrea...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1996.431974.x
更新日期:1996-03-01 00:00:00
abstract::We report a series of 20 patients with the myelodysplastic syndrome (MDS) each with a coexistent lymphoid or plasmacytic neoplasm. In none of the patients did chemotherapy play a part in the pathogenesis. The possible reasons for the coincidence of these conditions are discussed. The frequency and variety of associate...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1986.tb07505.x
更新日期:1986-05-01 00:00:00
abstract::Although individuals with sickle cell anaemia (SCA) have elevated baseline inflammation and endothelial activation, the acute phase response to maximal exercise has not been evaluated among children with SCA. We measured the acute phase response to maximal exercise testing for soluble vascular cell adhesion molecule (...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.13782
更新日期:2015-12-01 00:00:00
abstract::Juvenile haemochromatosis or haemochromatosis type 2 is a rare autosomal recessive disorder which causes iron overload at a young age, affects both sexes equally and is characterized by a prevalence of hypogonadism and cardiopathy. Patients with haemochromatosis type 2 have been reported in different ethnic groups. Li...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2141.2002.03509.x
更新日期:2002-06-01 00:00:00