Abstract:
:Although expressed in several haematological lineages and involved in multiple different signalling pathways, Bruton tyrosine kinase (BTK) plays an indispensible role in B cells in signalling from the B cell receptor (BCR) for antigen. Many B cell malignancies remain dependent on constitutive BCR signalling, making BTK a functional therapeutic target. Several BTK inhibitors (BTKi) with different kinomes and modes of action are being assessed clinically. This review documents the efficacy and toxicity of BTKi in chronic lymphocytic leukaemia (CLL). Clinically, the furthest in development is ibrutinib (trade name, Imbruvica), an irreversible BTKi, which has shown spectacular preliminary efficacy, with rapid reductions in lymph nodes accompanied by peripheral blood lymphocytosis. The lymphocytosis resolves slowly and most patients do not enter a complete remission. Nevertheless, it is possible to maintain many CLL patients, even those with adverse cytogenetic features, on drug for many months with minimal toxicities, thus potentially transforming the therapeutic paradigms for CLL. The efficacy, lack of toxicity and oral administration of BTKi will ensure their adoption in a wide range of B cell malignancies. An outstanding challenge is to incorporate BTKi with other precision medicines in a mechanism-based manner in order to dispense with conventional chemotherapy.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Hutchinson CV,Dyer MJdoi
10.1111/bjh.12895subject
Has Abstractpub_date
2014-07-01 00:00:00pages
12-22issue
1eissn
0007-1048issn
1365-2141journal_volume
166pub_type
杂志文章,评审abstract::Therapeutic options for treatment of recurrence of leukaemia after allogeneic bone marrow transplantation (BMT) are limited. A beneficial effect of donor lymphocyte infusions (DLI) has not previously been described in acute myeloid leukaemia (AML) relapse. We report a case of AML with t(8;21), relapsing 3 months after...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1996.d01-1477.x
更新日期:1996-02-01 00:00:00
abstract::Commercial preparations of ferritin inhibited reticulocyte-lysate cell-free protein synthesis and disaggregated polyribosomes to monoribosomes and ribosomal subunits. These effects were prevented by addition of reduced glutathione (GSH) to the incubation medium, but ferritin did not lower GSH concentration in the lysa...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1976.tb00962.x
更新日期:1976-04-01 00:00:00
abstract::We describe genetic, haematological and biochemical properties of a new mouse pigment mutant, cocoa (coa). Cocoa is a recessive mutation located on the centromeric end of chromosome 3 near the Car-2 locus. The mutation causes increased bleeding time accompanied by symptoms of platelet storage pool deficiency (SPD), in...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1988.tb02376.x
更新日期:1988-07-01 00:00:00
abstract::This is an historical account of the randomised trials in chronic lymphocytic leukaemia in the UK between the years 1978 to 2004, describing their gestation, the treatments used and the main lessons learnt. Those lessons include: (1) how best to use chlorambucil, which was the first effective treatment for CLL; (2) th...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.17159
更新日期:2020-11-01 00:00:00
abstract::The sensitivity to cytosine arabinoside (Ara-C) of blast progenitors from 22 acute myeloblastic leukaemia (AML) patients was studied in methylcellulose and suspension cultures. Primary colony-formation (PE1) in methylcellulose reflects the terminal divisions of blast progenitors, while secondary colony formation (PE2)...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1988.tb02462.x
更新日期:1988-10-01 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::Chemokines are a family of over 40 small (8 kDa) related proteins with the function of moving cells along a chemotactic gradient, either to organise cells within an organ or to facilitate the movement of leucocytes around the body. Mouse models have implicated the importance of the chemokine CXCL12 in haematopoiesis a...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2141.2005.05841.x
更新日期:2006-02-01 00:00:00
abstract::Children with Down syndrome have a 20- to 50-fold increased risk of acute lymphocytic or myeloid leukaemia. Whole or partial gains of chromosome 21 have been described in multiple childhood leukaemias, and have recently been reported as a likely primary event in B-precursor-acute lymphoblastic leukaemia. It is unclear...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2011.08985.x
更新日期:2012-04-01 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::Children with Down syndrome (DS) have a greater risk for developing both acute lymphoblastic leukaemia (ALL) and significant adverse effects of chemotherapy. We investigated their outcome with, and tolerance of, treatment protocols for relapsed ALL optimized in the paediatric population without DS. Probability of surv...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.12348
更新日期:2013-07-01 00:00:00
abstract::Current laboratory diagnostic methods for invasive fungal infection (IFI) in haemato-oncology patients are insensitive, resulting in late diagnosis and contributing to high mortality. In recent years, progress has been made in the development and evaluation of sensitive sero-diagnostic assays, including detection of g...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2141.2004.05031.x
更新日期:2004-08-01 00:00:00
abstract::Umbilical cord blood transplant (UCBT) is associated with impaired early immune reconstitution. This might be explained by a lower T-cell dose infused, the naivety of cord blood T-cells and the use of in vivo T-cell depletion. We studied the pattern of early immune reconstitution and the clinical outcome of children u...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2011.08994.x
更新日期:2012-03-01 00:00:00
abstract::Ibrutinib is associated with durable responses in patients with Waldenström macroglobulinaemia (WM). We hypothesized that response depth is predictive of progression-free survival (PFS) in WM patients treated with ibrutinib. Using landmark analyses, we evaluated response depth in two cohorts of WM patients treated wit...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.17225
更新日期:2020-11-18 00:00:00
abstract::Previous studies have established that protein kinase C-zeta (PKC-zeta) is critical for neuronal cell differentiation. However, the role of PKC-zeta in haematopoietic cell differentiation is less clear. In this study, we have investigated the influence of PKC-zeta overexpression on the phenotype of the human monocytic...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03625.x
更新日期:2002-08-01 00:00:00
abstract::FLT3-internal tandem duplication (ITD) mutations are heterogeneous with regards to length and proportion of DNA harbouring the mutation and the expression level of FLT3 also varies widely, however very little is known about the biological effects of these variables. We studied FLT3-associated biological parameters in ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2009.07901.x
更新日期:2009-12-01 00:00:00
abstract::A new alpha thalassemia defect has been detected in the South African population. Restriction mapping of the alpha globin gene cluster in affected individuals has established that the defect is associated with the removal of 22.8-23.7 kb of DNA, including the psi zeta 1, psi alpha 1, psi alpha 2, alpha 2 and alpha 1 g...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1987.tb01341.x
更新日期:1987-08-01 00:00:00
abstract::Peripheral blood stem cell autografts for the treatment of chronic myeloid leukaemia (CML) are currently under evaluation. A patient with CML received intensive chemotherapy followed by granulocyte colony-stimulating factor prior to the collection of peripheral blood derived stem cells. He developed unusually severe, ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1995.tb05172.x
更新日期:1995-06-01 00:00:00
abstract::To create immortal mesenchymal cell lines, we transduced primary human bone marrow mesenchymal cells with telomerase reverse transcriptase (TERT). TERT+ mesenchymal cells continued to grow for > 2 years; parallel TERT- cultures underwent senescence after 15 weeks. TERT+ mesenchymal cells did not form foci in soft agar...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2003.04217.x
更新日期:2003-03-01 00:00:00
abstract::A pilot trial was initiated for chronic myeloid leukaemia patients, which employed imatinib for remission induction, followed by reduced-intensity conditioning and an in vivo T-cell depleted graft. Out of nine patients, six experienced a molecular relapse and one patient had a haematological relapse at a median interv...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2141.2006.06404.x
更新日期:2007-01-01 00:00:00
abstract::The EGFP-tk retroviral vector, encoding enhanced green fluorescent protein (EGFP) and the herpes simplex virus thymidine kinase (HSV-tk) packaged in a Phoenix amphotropic cell line, was used to transduce healthy donor T lymphocytes. Infection yielded a mean of 41.8 +/- 9.3% SD (range 31.1-48.4%) EGFP-positive cells an...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.02264.x
更新日期:2000-09-01 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::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::MonoMAC is a complex primary immunodeficiency caused by mutations in the myeloid transcription factor GATA2, characterized by multilineage cytopenia with malignant complications and severe infections, including mycobacteria and herpesviruses. We describe the clinical presentation, genetics and antiviral inflammatory r...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.15947
更新日期:2019-08-01 00:00:00
abstract::Panobinostat in combination with bortezomib and dexamethasone demonstrated a significant and clinically meaningful progression-free survival benefit compared with placebo, bortezomib and dexamethasone in the phase 3 PANORAMA 1 (Panobinostat Oral in Multiple Myeloma 1) trial. Despite this benefit, patients in the panob...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1111/bjh.14821
更新日期:2017-10-01 00:00:00
abstract::We have investigated the control of lysozyme gene expression in HL-60 cells induced to differentiate into macrophage-like cells with phorbol myristate acetate (PMA). Differentiation, as evidenced by cellular adherence, and morphological changes corresponded temporally to an increase in nonspecific esterase activity. T...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1985.tb07380.x
更新日期:1985-05-01 00:00:00
abstract::Positron emission tomography using fluorine-18 (FDG-PET) is increasingly used in the staging and follow-up of malignant lymphomas, although its precise role has not yet been determined. This review considers the results reported at the different stages in the disease history and separately considers the major histolog...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2141.2004.05069.x
更新日期:2004-09-01 00:00:00
abstract::Experiments were performed to investigate the relative role of phospholipase A2 (PLA2) in the activation and cytokine-mediated priming of neutrophil superoxide production. PLA2 activity was measured with a radiometric assay which discriminates between PLA2 and the downstream enzyme, 5-lipoxygenase. In cells that had n...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1996.432970.x
更新日期:1996-03-01 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::Clinical management of chronic lymphocytic leukaemia (CLL) in patients aged ≥80 years is based on limited evidence due to the lack of published information. Therefore, we analysed CLL patients aged ≥80 years using data from seven phase III clinical trials of the German CLL Study Group. Among 3552 participants, 152 wer...
journal_title:British journal of haematology
pub_type: 杂志文章,meta分析
doi:10.1111/bjh.15604
更新日期:2018-12-01 00:00:00
abstract::The granulocytes of 23 patients with chronic granulocytic leukaemia were examined in the indirect immunofluorescence test and some also in the microleucoagglutination test, with specific alloantisera against the NA1, NA2, NB1 and ND1 antigens and a specific granulocyte xenoantiserum. In 10 cases a complete loss of all...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1979.tb03791.x
更新日期:1979-12-01 00:00:00