Abstract:
:β-thalassemia and sickle cell disease are widespread fatal genetic diseases. None of the existing clinical treatments provides a solution for all patients. Two main strategies for treatment are currently being investigated: (i) gene transfer of a normal β-globin gene; (ii) reactivation of the endogenous γ-globin gene. To date, neither approach has led to a satisfactory, commonly accepted standard of care. The δ-globin gene produces the δ-globin of hemoglobin A2. Although expressed at a low level, hemoglobin A2 is fully functional and could be a valid substitute of hemoglobin A in β-thalassemia, as well as an anti-sickling agent in sickle cell disease. Previous in vitro results suggested the feasibility of transcriptional activation of the human δ-globin gene promoter by inserting a Kruppel-like factor 1 binding site. We evaluated the activation of the Kruppel-like factor 1 containing δ-globin gene in vivo in transgenic mice. To evaluate the therapeutic potential we crossed the transgenic mice carrying a single copy activated δ-globin gene with a mouse model of β-thalassemia intermedia. We show that the human δ-globin gene can be activated in vivo in a stage- and tissue-specific fashion simply by the insertion of a Kruppel-like factor 1 binding site into the promoter. In addition the activated δ-globin gene gives rise to a robust increase of the hemoglobin level in β-thalassemic mice, effectively improving the thalassemia phenotype. These results demonstrate, for the first time, the therapeutic potential of the δ-globin gene for treating severe hemoglobin disorders which could lead to novel approaches, not involving gene addition or reactivation, to the cure of β-hemoglobinopathies.
journal_name
Haematologicajournal_title
Haematologicaauthors
Manchinu MF,Marongiu MF,Poddie D,Casu C,Latini V,Simbula M,Galanello R,Moi P,Cao A,Porcu S,Ristaldi MSdoi
10.3324/haematol.2012.082768subject
Has Abstractpub_date
2014-01-01 00:00:00pages
76-84issue
1eissn
0390-6078issn
1592-8721pii
haematol.2012.082768journal_volume
99pub_type
杂志文章相关文献
HAEMATOLOGICA文献大全abstract::A case of stiff-man syndrome (SMS), a rare and dramatic CNS disease characterized by continuous muscle activity and painful spasms resembling a chronic form of tetanus, occurring in a patient with Hodgkin's disease (HD) is reported. The patient developed the clinical features of SMS at the same time as the HD relapse....
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1990-11-01 00:00:00
abstract::HTLV-1 infections and their associated diseases are very rare in Italy, as well as in most parts of Europe, occurring prevalently in subjects related to endemic areas. The HTLV-1-associated leukemia/lymphoma, ATLL, is a very aggressive T-cell non-Hodgkin's lymphoma which can be difficult to recognize in non-endemic ar...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2003-07-01 00:00:00
abstract::Chronic autoimmune or pathogen-induced immune reactions resulting in lymphoid neogenesis are associated with development of malignant lymphomas, mostly extranodal marginal zone B-cell lymphomas (MZBCLs). In this review we address (i) chemokines and adhesion molecules involved in lymphoid neogenesis; (ii) the autoimmun...
journal_title:Haematologica
pub_type: 杂志文章,评审
doi:10.3324/haematol.2009.005983
更新日期:2009-08-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Our objective was to improve the outcome of cord blood (CB) transplantation in adults, by overcoming the limitations imposed by the low number of stem cells present in CB units. DESIGN AND METHODS:We combined single CB units and co-infusion of third party donor (TPD)-derived peripheral blood ...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2006-05-01 00:00:00
abstract:BACKGROUND:Granulocyte colony-stimulating factor mobilized peripheral blood stem cells are increasingly used instead of bone marrow as a stem cell source for transplantation. Whereas this change is almost complete for autologous transplantation, there are some concerns when considering allogeneic transplants. DESIGN A...
journal_title:Haematologica
pub_type: 杂志文章,多中心研究
doi:10.3324/haematol.2009.006924
更新日期:2009-09-01 00:00:00
abstract::Heart disease is the leading cause of mortality and one of the main causes of morbidity in beta-thalassemia. The clinical spectrum of the thalassemia syndrome ranges from the severe, transfusion--dependent thalassemia major and the asymptomatic carrier state. Thalassemia intermedia represents a milder form and is usua...
journal_title:Haematologica
pub_type: 杂志文章,评审
doi:10.3324/haematol.10915
更新日期:2007-05-01 00:00:00
abstract::We quantified Wilm's tumor gene (WT1) using a real time quantitative polymerase chain reaction in 20 adult patients with acute lymphoblastic leukemia at presentation. A WT1 level greater than 906 (median value for the whole series) was a significant predictor of a poor disease-free and overall survival in uni- and mul...
journal_title:Haematologica
pub_type: 信件
doi:
更新日期:2006-02-01 00:00:00
abstract::A case-control study was conducted among Italian children treated with a stem cell transplant (SCT). Cases (n = 43) were allogeneic recipients with osteonecrosis, and the controls (n = 129) were matched to the corresponding cases on the basis of survival, SCT center and date of transplant. Univariate analysis showed t...
journal_title:Haematologica
pub_type: 杂志文章,多中心研究
doi:
更新日期:2006-08-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Storage pool diseases (SPD) are heterogeneous disorders associated with an abnormal presence of intraplatelet granules, which cause mild to moderate bleeding diathesis. We investigated signaling through tyrosine phosphorylation of proteins occurring in platelets with total or partial absence o...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2002-06-01 00:00:00
abstract:BACKGROUND:The incidence of primary gastric non-Hodgkin's lymphoma (NHL) appears to have increased worldwide in recent years, and this seems to be confirmed by large-sample population studies. METHODS AND RESULTS:We derived our data from the Lombardy Cancer Registry, which provides the incidence of cancer in the provi...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
abstract::We analyzed the clinical outcome of 146 adult patients receiving an HLA-identical sibling donor stem cell transplant depending on HA-8 matching status. The presence of an HA-8 mismatch was associated with an increased risk of severe acute graft-versus-host disease and with a worse overall survival. ...
journal_title:Haematologica
pub_type: 信件
doi:
更新日期:2005-12-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Transplant-related mortality (TRM) following allogeneic hematopoietic stem cell transplantation (HSCT) has been reported to be related to disease stage, duratiion of disease and type of donor. Furthermore, the outcome of transplants performed in the 1990s appears to be better than that of tran...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2004-10-01 00:00:00
abstract::Diabetes insipidus and thrombocytosis were presenting symptoms in a case of adult ANLL-M1. Cytogenetic investigations revealed a typical 3q rearrangement, i.e. inv(3)(q21q26). A subclone with monosomy 7 was also found and documented by FISH analysis. Correlations between clinical/hematological features and cytogenetic...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) showed recurrent rearrangement of the BCL6 which is gene detected in 48% of cases analyzed by interphase-fluorescent in situ hybridization (FISH). These findings point to a critical role for BCL6 in the development of this distinct Hodg...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2004-08-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Graft-versus-host disease (GVHD) presents an important complication of allogeneic bone marrow transplantation. A method to predict GVHD might be the analysis of cytotoxic T lymphocyte precursors, but the technique requires the use of radioactive elements not suitable in all laboratories. DESIG...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:1998-08-01 00:00:00
abstract::Renewing interest in cancer immunotherapy reflects the excellent results that have been obtained in animal models and the promising results in early clinical trails with dendritic cell (DC) based approaches. The central role that DCs play in the initiation of an immune response raises the possibility of using them to ...
journal_title:Haematologica
pub_type: 杂志文章,评审
doi:
更新日期:2000-02-01 00:00:00
abstract::New drugs are needed for the treatment of relapsed acute lymphoblastic leukemia and preclinical evaluation of the MEK inhibitor, selumetinib, has shown that this drug has excellent activity in those leukemias with RAS pathway mutations. The proapoptotic protein, BIM is pivotal in the induction of cell death by both se...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2017.185975
更新日期:2019-09-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:The diagnosis of myelodysplastic syndromes (MDS) is essentially morphological and based on the presence of dysplastic features in the peripheral blood and bone marrow. The French-American-British (FAB) Cooperative Group proposed a classification based on easily obtainable laboratory information...
journal_title:Haematologica
pub_type: 杂志文章,评审
doi:
更新日期:1998-03-01 00:00:00
abstract::Forty-six patients with chronic myeloid leukemia receiving imatinib mesylate (39 in chronic phase, one in accelerated phase, and six in blastic crisis), were studied for a 20-62 month follow-up period by cytogenetics and fluorescence in situ hybridization using dual-color, dual-fusion BCR and ABL probes. This approach...
journal_title:Haematologica
pub_type: 信件
doi:
更新日期:2006-07-01 00:00:00
abstract::Dickkopf-1 (DKK1), broadly expressed by tumor cells from human multiple myeloma (MM) and other cancers but absent from most normal tissues, may be an ideal target for immunotherapy. Our previous studies have shown that DKK1 (peptide)-specific cytotoxic T lymphocytes can effectively lyse primary MM cells in vitro. To d...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2019.236836
更新日期:2020-02-20 00:00:00
abstract::Aberrant expression of aurora kinase A is implicated in the genesis of various neoplasms, including acute myeloid leukemia. Alisertib, an aurora A kinase inhibitor, has demonstrated efficacy as monotherapy in trials of myeloid malignancy, and this efficacy appears enhanced in combination with conventional chemotherapi...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2016.158394
更新日期:2017-04-01 00:00:00
abstract::POEMS syndrome is a rare clonal plasma cell disease. Patients with POEMS syndrome are at risk of developing pulmonary hypertension, but the data on its incidence and impact on outcome are limited. We reviewed records of 154 POEMS syndrome patients with complete duplex echocardiography data for estimation of pulmonary ...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2012.073031
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Loss of heterozygosity (LOH) on the long arm of chromosome 7 (7q) has been frequently reported in several types of human cancer including hematologic malignancies. Moreover, monosomy of chromosome 7 and 7q deletions have been associated in acute myeloid leukemia (AML) with aggressive disease a...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2003-04-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Although acquired aplastic anemia is usually a chronic disorder, a small proportion of patients with aplastic anemia was reported to recover spontaneously without specific therapy such as allogeneic bone marrow transplantation or immunosuppressive treatment. We attempted to determine the rate ...
journal_title:Haematologica
pub_type: 杂志文章
doi:
更新日期:2001-09-01 00:00:00
abstract::Differentiation of erythroblasts to mature red blood cells involves dynamic changes of the membrane and cytoskeleton networks that are not fully characterized. Using a mouse fetal liver erythroblast culture system and a targeted shRNA functional screening strategy, we identified a critical role of pleckstrin-2 in acti...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2014.105809
更新日期:2014-07-01 00:00:00
abstract::Indoleamine 2,3-dioxygenase degrades the amino acid tryptophan which is essential for T cells. Tryptophan depletion causes T-cell cycle arrest and solid tumors that express high levels of indoleamine 2,3-dioxygenase can create immune suppression. Recently, blasts of patients with acute myeloid leukemia were shown to e...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.13113
更新日期:2008-12-01 00:00:00
abstract::e tested whether polymorphic variations in glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) and interleukin-1 (IL-1beta and IL-1RN) genes confer susceptibility to mucosa-associated lymphoid tissue lymphomas (MALT) in a Chinese population. The rates of GSTM1, GSTP1, IL-1beta and IL-1RN genotypes did not differ bet...
journal_title:Haematologica
pub_type: 信件
doi:
更新日期:2004-08-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Peripheral blood stem cells (PBSC) following reduced intensity conditioning (RIC) are being increasingly used for allogeneic transplantation in multiple myeloma. The purpose of this study was to compare outcome of patients transplanted with either PBSC or bone marrow (BM) following RIC or myel...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.11353
更新日期:2007-11-01 00:00:00
abstract::Fibrinogen is an abundant protein synthesized in the liver, present in human blood plasma at concentrations ranging from 1.5-4 g/L in healthy individuals with a normal half-life of 3-5 days. With fibrin, produced by thrombin-mediated cleavage, fibrinogen plays important roles in many physiological processes. Indeed, t...
journal_title:Haematologica
pub_type: 杂志文章,评审
doi:10.3324/haematol.2019.236901
更新日期:2020-01-31 00:00:00
abstract::Iron recycling by macrophages is essential for erythropoiesis, but may also be relevant for iron redistribution to neighboring cells at the local tissue level. Using mice with iron retention in macrophages due to targeted inactivation of the iron exporter ferroportin, we investigated the role of macrophage iron releas...
journal_title:Haematologica
pub_type: 杂志文章
doi:10.3324/haematol.2018.197517
更新日期:2019-01-01 00:00:00