Abstract:
:Induction of fetal haemoglobin (HbF) is a promising therapeutic approach for the treatment of β-thalassaemia and sickle cell disease (SCD). Several pharmacological agents, such as hydroxycarbamide (HC) and butyrates, have been shown to induce the γ-globin genes (HBG1, HBG2). However, their therapeutic use is limited due to weak efficacy and an inhibitory effect on erythroid differentiation. Thus, more effective agents are needed. The histone deacetylase (HDAC) inhibitors are potential therapeutic haemoglobin (Hb) inducers able to modulate gene expression through pleiotropic mechanisms. We investigated the effects of a HDAC inhibitor, Givinostat (GVS), on erythropoiesis and haemoglobin synthesis and compared it with sodium butyrate and HC. We used an in vitro erythropoiesis model derived from peripheral CD34⁺ cells of healthy volunteers and SCD donors. GVS effects on erythroid proliferation and differentiation and on Hb synthesis were investigated. We found that GVS at high concentrations delayed erythroid differentiation with no specific effect on HBG1/2 transcription. At a low concentration (1 nmol/l), GVS induced Hb production with no effects on cells proliferation and differentiation. The efficacy of GVS 1 mol/l in Hb induction in vitro was comparable to that of HC and butyrate. Our results support the evaluation of GVS as a new candidate molecule for the treatment of the haemoglobinophathies due to its positive effects on haemoglobin production at low and non-toxic concentrations.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Ronzoni L,Sonzogni L,Fossati G,Modena D,Trombetta E,Porretti L,Cappellini MDdoi
10.1111/bjh.12814subject
Has Abstractpub_date
2014-06-01 00:00:00pages
714-21issue
5eissn
0007-1048issn
1365-2141journal_volume
165pub_type
杂志文章abstract::Myeloid neoplasms derive from the pathological clonal expansion of an abnormal stem cell and span a diverse spectrum of phenotypes including acute myeloid leukaemia (AML), myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS). Expansion of myeloid blasts with suppression of normal haematopoiesis is th...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2141.2010.08525.x
更新日期:2011-03-01 00:00:00
abstract::This review article acknowledges the pioneering contribution of William Bate Hardy in shaping the concept of mast cell heterogeneity. In two outstanding papers, published in 1894 and 1895, he focussed on the 'wandering cells' (the modern leucocytes) in different mammalian species and distinguished two types of granula...
journal_title:British journal of haematology
pub_type: 传,历史文章,杂志文章
doi:10.1111/j.1365-2141.2009.07938.x
更新日期:2010-07-01 00:00:00
abstract::To determine the effects of L-arginine (L-Arg) supplementation on nitric oxide metabolite (NOx) production, oral L-Arg was given to normal controls, sickle cell disease (SCD) patients at steady state and SCD patients hospitalized with a vaso-occlusive crisis (VOC). L-Arg (0.1 g/kg) increased NOx formation by 18.8 +/- ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.02403.x
更新日期:2000-11-01 00:00:00
abstract::Double-negative (DN) regulatory T cells (Tregs) are specialized T lymphocytes involved in the down-modulation of immune responses, resulting in allotolerance after allogeneic haematopoietic stem cell transplantation (HSCT). Most of the properties of DN Tregs were identified in murine models, including the unique abili...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2008.07021.x
更新日期:2008-04-01 00:00:00
abstract::The Abl kinase inhibitor STI571 (imatinib mesylate) induces haematological remissions in many patients with chronic myeloid leukaemia (CML) but advanced stage CML usually becomes resistant to STI571. We describe a patient in whom progressive resistance to STI571 correlated with the appearance of a mutation in the Bcr-...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03708.x
更新日期:2002-10-01 00:00:00
abstract::The clonalities in white blood cells (WBC) of blood and nucleated bone marrow cells from patients with refractory anaemia and aplastic anaemia were examined by polymerase chain reaction (PCR) methods using the polymorphic short tandem repeat (STR) on the human androgen-receptor gene (HUMARA). Peripheral blood samples ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1995.tb08422.x
更新日期:1995-04-01 00:00:00
abstract::The plasma concentrations of erythropoietin (Ep), soluble transferrin receptors (sTfRs), iron, total iron binding capacity (TIBC) and ferritin were monitored in five leukaemia patients undergoing autologous bone marrow stem cell transplantation (BMSCT) and in 10 lymphoma and 21 ovarian cancer patients undergoing autol...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1997.d01-2104.x
更新日期:1997-03-01 00:00:00
abstract::A multiparameter flow-cytometrical method for the quantitation of CD34(+)-cells present in adult human peripheral blood cells (PBMC) has been developed. PBMC from 13 healthy adult subjects were analysed for CD34(+)-cells by flow-cytometry, with only the lymphoid population of cells negative for anti-CD3-moAb included ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1991.tb08609.x
更新日期:1991-04-01 00:00:00
abstract::Smoking causes atherosclerosis, and smokers have increased thromboxane (TXA2) formation. As aspirin inhibits TXA2 production we speculated that smokers would preferentially profit from inhibition of the TXA2 pathway by aspirin. Increased expression of P-selectin, a constituent of the alpha-granules of platelets, and i...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1998-09-01 00:00:00
abstract::Tissue factor pathway inhibitor (TFPI) is released to circulating blood after intravenous (i.v.) and subcutaneous (s.c.) injections of heparins, and may thus contribute to the antithrombotic effect of heparins. We have recently shown that total TFPI activity, plasma free TFPI antigen, and heparin releasable TFPI were ...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1999-12-01 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::Adhesive interactions between haemopoietic progenitor cells and bone marrow sinusoidal endothelium are potentially important in the homing of these cells back to the extravascular compartment of the marrow to re-establish haemopoiesis following stem cell transplantation. A simple method for the isolation and culture o...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1994.tb05128.x
更新日期:1994-12-01 00:00:00
abstract::Down syndrome (DS) children have a 10-20-fold increased risk of developing ALL or AML compared to non-DS children. An increased disomic homozygosity of the polymorphic DNA markers in the pericentromeric region of chromosome 21q (21q11) has repeatedly been found in DS patients with ANLL-M7 and DS-specific transient abn...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.00924.x
更新日期:1998-10-01 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
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abstract::Excessive bleeding represents a major complication of surgical interventions and its control is especially relevant in patients with Congenital Bleeding Disorders (CBD). In factor VII (FVII) deficiency, scanty data on surgery is available to guide treatment strategies. The STER (Seven Treatment Evaluation Registry) is...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2010.08287.x
更新日期:2011-02-01 00:00:00
abstract::We report outcomes after myeloablative haematopoietic cell transplantation (HCT) from human leucocyte antigen (HLA)-matched sibling donors in 67 patients with sickle cell disease transplanted between 1989 and 2002. The most common indications for transplantation were stroke and recurrent vaso-occlusive crisis in 38% a...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2141.2007.06592.x
更新日期:2007-06-01 00:00:00
abstract::This placebo-controlled study evaluated the efficacy of Flt-3 ligand (FL) combined with TPO in myelosuppressed rhesus monkeys. The monkeys were subjected to 5 Gy total body irradiation (TBI), resulting in 3 weeks of profound pancytopenia, and received either 5 microg/kg of rhesus TPO i.v. on d 1 (n = 4) and 100 microg...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2003.04283.x
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abstract::Recently, leukaemia-associated antigens (LAA) recognized by T lymphocytes, such as Wilm's tumour-1 (WT-1) or pathogenesis-related protein-1 (PR-1), have been identified. For immunotherapies that employ antigen peptides, either alone or pulsed on dendritic cells (DC), the expression of human leucocyte antigen (HLA) mol...
journal_title:British journal of haematology
pub_type: 杂志文章
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abstract::To resolve the controversy concerning the role of p53 in the killing of resting lymphocytes by purine nucleoside analogues, we examined the cytotoxic effects of chlorodeoxyadenosine, fludarabine and deoxycoformycin (plus deoxyadenosine) on unstimulated spleen cells from p53-knockout versus wild-type mice. p53-knockout...
journal_title:British journal of haematology
pub_type: 杂志文章
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abstract::Bone marrow culture in a patient with aplastic anaemia responding to anabolic steroid (methandienone) therapy, showed an unusually high degree of growth in unstimulated cultures. Growth in unstimulated cultures is due to factors with colony stimulating activity (CSA) released by monocyte macrophages in the bone marrow...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1977.tb00990.x
更新日期:1977-08-01 00:00:00
abstract::Enlarged lymph nodes may be a marker of occult cancer, but accurate data on cancer risk are limited. We used population-based Danish medical registries to assess cancer risk in a cohort of patients with a first-time inpatient or outpatient hospital contact for enlarged lymph nodes during 1994-2008. Observed cancer inc...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.12174
更新日期:2013-03-01 00:00:00
abstract::A serial study of coagulation activation and whole-blood viscosity was performed on 37 patients with local or systemic bacterial infection, malaria, or a viral infection. Thrombocytopenia, without consumption of coagulation factors, was the main feature of benign tertian malaria and viral infection, whereas in septica...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1979.tb01155.x
更新日期:1979-07-01 00:00:00
abstract::The role of antiphospholipid antibodies in the pathogenesis of the thrombocytopenia observed during primary antiphospholipid antibody syndrome (APAS) and systemic lupus erythematosus (SLE) remains controversial. We have used the MAIPA test to examine the frequency and specificity of anti-platelet antibodies directed a...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1997.2243038.x
更新日期:1997-08-01 00:00:00
abstract::There are no accepted methods to predict the development of platelet transfusion refractoriness (PTR) due to human leucocyte antigen (HLA)-alloimmunization. Hence, matched platelets are usually given only to patients demonstrating PTR, necessarily resulting in some ineffective random donor platelets (RDPLT) transfusio...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.12369
更新日期:2013-08-01 00:00:00
abstract::Mantle-cell lymphoma (MCL) is a B-cell tumour with a usually poor prognosis, characterized by the proliferation of small cleaved lymphocytes with a diffuse growth pattern. We report a polymerase chain reaction-based analysis of minimal residual disease in a patient who achieved complete remission after allogeneic bloo...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1996.d01-1816.x
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abstract::Second primary malignancies have long been associated with chronic lymphocytic leukaemia (CLL). We assessed secondary tumour samples from CLL and control patients for the presence of human papilloma virus (HPV). 132 CLL patients with 44 second malignancies were compared to a matched randomly-identified control populat...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2010.08110.x
更新日期:2010-05-01 00:00:00
abstract::We analysed the results of haematopoietic cell transplantation (HCT) in 30 patients aged 60-78 (median 65) years, with primary myelofibrosis or myelofibrosis evolving from antecedent polycythaemia vera or essential thrombocythaemia. Donors were human leucocyte antigen (HLA)-identical siblings (N = 15) or unrelated ind...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2011.08582.x
更新日期:2011-04-01 00:00:00
abstract::The activities of glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP oxidoreductase, G6PD), 6 phosphate glucono dehydrogenase (6 phospho-D-gluconate: NADP oxidoreductase, 6PGD) lactate dehydrogenase (D-lactate: NAD oxidoreductase, LDH), glutamate oxaloacetate transaminase (L-aspartate: 2-oxo-glutarate amin...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1976.tb00176.x
更新日期:1976-09-01 00:00:00
abstract::The process of tumorigenesis is frequently associated with resistance to growth inhibition by physiological regulators of normal cells. Murine macrophage-like cell lines BAC1.2F5, RAW264, J774.1A and PU5/1.8 were resistant to growth inhibition by bacterial lipopolysaccharide (LPS) and pertussis toxin, agents that bloc...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1993.tb03092.x
更新日期:1993-07-01 00:00:00
abstract::Dendritic cells (DC) are attractive candidates for use in vaccine-based immunotherapy. We have analysed the functional capability of DC generated in vitro from blood CD14(+) cells of chronic lymphocytic leukaemia (CLL) patients and healthy donors by culturing for 10 d with granulocyte-macrophage colony-stimulating fac...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2001.03117.x
更新日期:2001-11-01 00:00:00