Abstract:
:Deregulated Hedgehog (Hh) signalling activity may be associated with a broad range of cancer types and hence has become an attractive target for therapeutic intervention. Although initial haematological interest focused on the therapeutic targeting of this pathway in chronic myeloid leukaemia), small molecule inhibitors targeting the Hh pathway are now being tested in a range of other myeloid disorders, including myelofibrosis, myelodysplasia and acute myeloid leukaemia. In this review we will evaluate the rationale for targeting of the Hh pathway in myeloid diseases and discuss the novel agents that have entered the clinical arena. We will discuss pre-clinical models, emerging clinical trial data, and suggest how these targeted therapies may address current unmet medical needs. Finally, we will explore potential limitations of these therapies due to the emergence of secondary resistance mechanisms and speculate on future developments within this arena.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Khan AA,Harrison CN,McLornan DPdoi
10.1111/bjh.13426subject
Has Abstractpub_date
2015-08-01 00:00:00pages
323-35issue
3eissn
0007-1048issn
1365-2141journal_volume
170pub_type
杂志文章,评审abstract::Therapeutic plasma exchange (TPE) has been mainly used in the treatment of autoimmune diseases. The main mechanisms of action of TPE include the removal of circulating autoantibodies, immune complexes, complement components, cytokines and adhesion molecules, along with sensitization of antibody-producing cells to immu...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/bjh.15903
更新日期:2019-07-01 00:00:00
abstract::Although haematopoietic cell transplantation (HCT) is curative for sickle cell anaemia (SCA), concerns about its short- and long-term toxicities limit its application. A potential toxicity is an adverse effect on growth. To identify an HCT growth effect, serial height and weight measurements from 53 children and adole...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2141.2006.06486.x
更新日期:2007-02-01 00:00:00
abstract::The Sysmex SE-9500 automated cell counter provides an estimate of immature cells referred to as 'haemopoietic progenitor cells' (HPC). The aim of this study was to relate the HPC count to CD34+ cell levels in mobilized peripheral blood and to determine whether the HPC count was valuable in predicting apheresis yields ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1999.01584.x
更新日期:1999-08-01 00:00:00
abstract::In an effort to clarify the effect of human T cell leukaemia virus type I (HTLV-I) infection on virus-specific CD8+ cytotoxic T cells, a herpes simplex virus-specific CD8+ cytotoxic T cell clone was infected with HTLV-I in vitro. The cytotoxic activity of the clone was found to have declined early after HTLV-I infecti...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1991.tb08576.x
更新日期:1991-03-01 00:00:00
abstract::The inducibility of glycosyl-phosphatidylinositol (GPI)-anchored proteins on affected paroxysmal nocturnal haemoglobinuria (PNH) neutrophils (PMN) after both in vitro and in vivo stimulation was investigated. Fc gamma R-III (CD16), decay-accelerating factor (DAF/CD55) and 20 kD homologous restriction factor (HRF20/CD5...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1993.tb03107.x
更新日期:1993-07-01 00:00:00
abstract::This study was undertaken to evaluate the toxicity and pharmacokinetics of a dimethyl sulphoxide (DMSO)-based intravenous formulation of busulphan in the conditioning of 45 patients undergoing allogeneic or autologous stem cell transplantation (SCT). Busulphan was given as a single daily dose. In 15 patients a single ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2001.03044.x
更新日期:2001-09-01 00:00:00
abstract::The molecular basis of the three major alleles (Fy(a)/Fy(b)/Fy) of the Duffy (FY) blood group system has recently been established but the Fy(x) phenotype associated with weak expression of the Fy(b) and other FY antigens is poorly understood. In the Fy(x) genes of five unrelated British and Swedish donors with the Fy...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.01083.x
更新日期:1998-12-01 00:00:00
abstract::The role of autologous stem cell transplantation (ASCT) and the optimal timing of such transplants in patients with follicular lymphoma (FL) remains contentious. We present a single-centre experience documenting the outcomes of 70 FL patients who underwent BEAM (carmustine, cytarabine, etopside, melphalan)-conditioned...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.12741
更新日期:2014-05-01 00:00:00
abstract::Prior studies indicate that neutrophil extracellular traps (NETs) are associated with arterial thromboembolism (ATE) and mortality. We investigated the association between NET formation biomarkers (citrullinated histone H3 [H3Cit], cell-free DNA [cfDNA], and nucleosomes) and the risk of ATE and all-cause mortality in ...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/bjh.15906
更新日期:2019-07-01 00:00:00
abstract::Thrombomodulin (TM) is an endothelial cell glycoprotein that acts as an anticoagulant. Mutation in the TM gene is a potential risk factor for thrombosis. The first TM mutation identified was a heterozygous substitution of T for G at nucleotide position 1456, which predicted Asp468 with Tyr in a Ser/Thr-rich domain. To...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1999.01567.x
更新日期:1999-08-01 00:00:00
abstract::Major histocompatibility complex class I molecule expression is reduced in some malignant tumours permitting escape from immune surveillance and is therefore associated with a poor prognosis. Seven cases of non-Hodgkin lymphomas out of 300 cases of malignant lymphoproliferative disorders totally lacked expression of c...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.00631.x
更新日期:1998-03-01 00:00:00
abstract::The question as to whether autologous stem cell transplantation (SCT) after consolidation chemotherapy improves the probability of survival of patients with acute myeloid leukaemia (AML) in first remission has not been settled. Here, we present the results of a phase III study conducted in newly diagnosed adult AML pa...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2141.2004.05282.x
更新日期:2005-01-01 00:00:00
abstract::Antithrombin III (AT) levels from normal and AT deficiency persons were measured by electroimmunoassay (EIA) and the results compared with a chromogenic assay (S2238). Discrepant results were obtained when plasma and serum were compared using one antiserum, and therefore did not always relate to functional activity. A...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1980.tb05967.x
更新日期:1980-10-01 00:00:00
abstract::We recently identified a human minor histocompatibility (H) antigen, encoded by UDP glycosyltransferase 2 family, polypeptide B17 (UGT2B17), whose immunogenicity results from differential expression in donor and recipient cells as a consequence of a homozygous deletion of the UGT2B17 gene. UGT2B17 is highly expressed ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2005.05427.x
更新日期:2005-04-01 00:00:00
abstract::Children with neutropenia of more than 3 months duration often have evidence of immune-mediated destruction of mature neutrophils and variable abnormalities of myeloid precursors in their bone marrow. These patients often have anti-neutrophil antibodies which persist for several months. To further investigate the aeti...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1993.tb08645.x
更新日期:1993-09-01 00:00:00
abstract::Conflicting evidence exists on the epidemiology of type 2 diabetes mellitus (T2DM) among patients with sickle cell disease (SCD). This study measured the prevalence, incidence and clinical outcomes associated with T2DM in a large US population of commercially-insured adults aged ≥20 years with SCD between 2009 and 201...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.15773
更新日期:2019-04-01 00:00:00
abstract::Immune reconstitution was studied prospectively in 66 children who underwent 77 haematopoietic cell transplantations (HCT): 46 autologous HCTs in 39 patients and 31 allogeneic HCTs in 27 patients. We studied the dynamic analysis of immune recovery with regard to potential factors affecting its speed, including age, ty...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03560.x
更新日期:2002-07-01 00:00:00
abstract::In an attempt to compare the sensitivity of bone radiographs and bone marrow magnetic resonance (MR) imaging for bone lesion detection in patients with stage III multiple myeloma (MM) and to evaluate the possible consequences of the replacement of the conventional radiographic skeletal survey (RSS) by an MR survey of ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1999.01529.x
更新日期:1999-07-01 00:00:00
abstract::Haem biosynthesis is the most important destination for absorbed iron, hence it can be hypothesized that iron absorption regulation should be integrated with haem metabolism. As an initial step to test this hypothesis, the effect on iron absorption of Tin-mesoporphyrin (SnMP), inhibitor of haem oxygenase, altering hae...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2003.04376.x
更新日期:2003-07-01 00:00:00
abstract::The effects of oral contraceptive (OC) usage on platelet responsiveness to arachidonic acid metabolites was investigated. Platelets obtained from women who had been taking oral contraceptives for at least 3 months were compared with those of age-matched controls. Both the basal and prostacyclin (PGI2)-stimulated plate...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1984.tb06090.x
更新日期:1984-10-01 00:00:00
abstract::This study aimed to assess the potential of human cord blood (CB) cells to engraft in the xenogenic non-obese diabetic/severe combined immunodeficient (NOD/SCID) mouse model after in vitro expansion culture. We also studied the quality of human haemopoiesis arising from the transplantation of fresh or expanded cells i...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03254.x
更新日期:2002-01-01 00:00:00
abstract::Fibrinogen Chapel Hill II is a hereditary, abnormal fibrinogen which is characterized by poor substrate reactivity toward thrombin, factor XIIIa and plasmin. The patient has a low plasma level of clottable protein with normal antigen concentration, high amounts of fibrinogen related material in serum, and prolonged th...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1982.tb03859.x
更新日期:1982-09-01 00:00:00
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 fr...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2009.07667.x
更新日期:2009-06-01 00:00:00
abstract::A 2-year-old girl is described with severe haemophilia A (factor VIII: C < 0.01 units/ml). Both of her parents were phenotypically normal. Cytogenetic analysis on the proband demonstrated an interstitial X chromosome deletion encompassing Xq26-q28. Molecular studies with several polymorphic markers close to and within...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1995.tb05213.x
更新日期:1995-08-01 00:00:00
abstract::Up-regulation of Fas/APO-1 (CD95) on haematopoietic progenitors and Fas-mediated apoptosis have been suggested to occur in a possible pathological mechanism in some bone marrow failure syndromes. We examined the expression of Fas antigen and susceptibility to Fas-mediated suppression of donor-derived haematopoietic ce...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.02022.x
更新日期:2000-05-01 00:00:00
abstract::Mastocytosis is a rare disease with varied presentation, myriad symptomatology and variable prognosis. Most patients present with cutaneous disease and mediator-related symptomatology with a small subset having systemic disease (systemic mastocytosis, SM). A subset of the latter develops synchronous or metachronous ha...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/bjh.16288
更新日期:2020-03-01 00:00:00
abstract::Platelets have recently been shown to trigger intrinsic coagulation by two alternative pathways, protect active clotting factors from inactivation by plasma inhibitors and catalyse intrinsic coagulation reactions on the platelet surface to form fibrin. To determine whether these platelet coagulant activities (PCA) mig...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2141.1976.tb00946.x
更新日期:1976-03-01 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::Tellurite (K2TeO3) has been suggested as a potential anti-sickling compound because it causes a selective increase in the water content of RBC. To investigate the conditions underlying the increase in RBC volume due to tellurite, normal RBCs were incubated with the compound in a physiological medium and the cells wash...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1988.tb02496.x
更新日期:1988-11-01 00:00:00
abstract::This study assessed the relevance of 2013 European LeukaemiaNet (ELN) response categories on patients treated with common frontline tyrosine kinase inhibitors (TKI) in chronic myeloid leukaemia in chronic phase (CML-CP). Four hundred and eighty-seven patients treated with imatinib (400 mg; IM 400, n = 70; 800 mg; IM80...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1111/bjh.13936
更新日期:2016-04-01 00:00:00