Abstract:
OBJECTIVE:Diamond-Blackfan anemia (DBA) is a rare congenital hypoplastic anemia caused by mutations in ribosomal protein (RP) genes. Our aim is to develop gene therapy for DBA patients with mutations in RPS19. We previously demonstrated that RPS19 gene transfer partially corrects erythroid development in vitro. In this study, we asked if RPS19 gene transfer corrects erythroid development in unsorted cells transplanted to immunodeficient mice and if the RPS19-corrected fraction has a proliferative advantage after transplantation. We further determined if high level of RPS19 expression is required for correction. MATERIAL AND METHODS:Mobilized peripheral blood CD34(+) cells were transduced by oncoretroviral vector particles pseudotyped with the feline endogenous retrovirus envelope. Vectors containing two different promoters with different RPS19 transgene expression levels were compared. Transduced cells were transplanted to immunocompromised nonobese diabetic/severe combined immunodeficient-beta2 microglobulin null mice in order to assess therapeutic effects of RPS19 gene transfer in vivo. RESULTS:We show that correction of erythroid development requires high RPS19 expression. The corrected fraction of unselected DBA cells have a survival advantage in vivo, suggesting that successful gene therapy may only require correction of a fraction of the patient cells. CONCLUSION:Our findings are fundamental for development of clinical gene therapy for DBA because they demonstrate increased engraftment of RPS19-transduced cells without selection of gene-corrected cells prior to transplantation, an essential prelude to studying long-term therapeutic effects in emerging animal models for DBA.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Flygare J,Olsson K,Richter J,Karlsson Sdoi
10.1016/j.exphem.2008.06.012subject
Has Abstractpub_date
2008-11-01 00:00:00pages
1428-35issue
11eissn
0301-472Xissn
1873-2399pii
S0301-472X(08)00310-Xjournal_volume
36pub_type
杂志文章abstract::The presence of multilineage dysplasia (MLD) by morphology at diagnosis in acute myeloid leukemia (AML) defines a separate subset in the World Health Organization classification with still-debated prognostic value. A major controversy concerns MLD's role in NPM1-mutated (NPM1⁺) AML, which correlates with good prognosi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2015.06.003
更新日期:2015-10-01 00:00:00
abstract:OBJECTIVE:Mesenchymal stem cells (MSCs) are capable of modulating the immune system through interaction with a wide range of immune cells. This study investigates the hypothesis that interaction of MSCs with macrophages could play a significant role in their antiinflammatory/immune modulatory effects. MATERIALS AND ME...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.09.004
更新日期:2009-12-01 00:00:00
abstract::An increase in triglyceride synthesis has been observed in cultures of human bone marrow fibroblasts after the cells reach confluence. The addition of hydrocortisone further enhances triglyceride synthesis. Conditioned medium from confluent cultures also stimulates adipogenesis, probably mediated by a factor released ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-03-01 00:00:00
abstract:OBJECTIVE:Mice harboring c-Myb hypomorphic mutations display enhanced thrombopoiesis because of increased numbers of megakaryocytes and their progenitors. Thrombopoietin induces these same effects, which lead us to hypothesize that the hormone acts through modulation of c-Myb expression, as c-Myb levels falls during th...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.07.001
更新日期:2008-12-01 00:00:00
abstract::Mouse bone marrow cells were cultured to determine some basic characteristics of the diffusion chamber (DC) technique. The main findings were as follows: (i) Incorporated 3H-thymidine was conveniently measured after deposition of a cell sample on glass fibre discs followed by methanol washing. Varying the specific act...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1975-08-01 00:00:00
abstract:OBJECTIVE:Donor T cells expressing lymph node homing receptors are the foremost initiators of acute graft-vs-host disease (aGVHD), and a high proportion of CD4(+)CCR7(+) T cells in human leukocyte antigen-matched allografts has been shown to confer a high risk of aGVHD without interfering in other outcomes. METHODS:Na...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2007.03.006
更新日期:2007-06-01 00:00:00
abstract::We evaluated the role of high-dose granulocyte colony stimulating factor (G-CSF) in vitro, in inducing the generation of high-proliferative potential colony forming cells (HPP-CFC), from either mononuclear cells or purified CD34+ cells. Both normal controls and patients undergoing peripheral blood stem cell (PBSC) mob...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1997-06-01 00:00:00
abstract::Megakaryocytes have been implicated in the micro-environmental abnormalities associated with fibrosis and hematopoietic failure in the bone marrow (BM) of primary myelofibrosis (PMF) patients, the Philadelphia-negative myeloproliferative neoplasm (MPN) associated with the poorest prognosis. To identify possible therap...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2019.10.001
更新日期:2019-11-01 00:00:00
abstract::Injection of mice with either natural bovine bone-derived or human recombinant transforming growth factor beta 1 (TGF-beta 1) resulted in a significant increase of the macrophage and macrophage-granulocyte-forming capacity of their macrophage colony-stimulating factor (M-CSF)- and granulocyte-macrophage colony-stimula...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1992-05-01 00:00:00
abstract:OBJECTIVE:CD34(+) cells, present within the bone marrow, have previously been shown to possess pancreatic endocrine potential. Based on this observation, we explored the capacity of CD34(+) cells derived in culture from the differentiation of human embryonic stem cells (hESC), for their in vivo pancreatic endocrine cap...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.03.002
更新日期:2010-06-01 00:00:00
abstract::Protein kinase activities are involved in cellular proliferation and differentiation, and inhibitors of these activities are useful for studying the mechanisms of induction of differentiation. We found that staurosporine, an inhibitor of protein kinase activities, induced morphological differentiation of human myelobl...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-07-01 00:00:00
abstract::Sustained NF-κB activation is often observed in acute myeloid leukemia (AML); therefore, proteasome inhibition has been proposed to efficiently target AML cells. In this study, we questioned whether leukemic stem cell-enriched CD34(+) cells are sensitive to the proteasome inhibitor bortezomib. Surprisingly, we observe...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2013.02.002
更新日期:2013-06-01 00:00:00
abstract::Granulocyte colony-stimulating factor (G-CSF) is used routinely in the clinical setting to mobilize hematopoietic stem progenitor cells (HSPCs) into the patient's blood for collection and subsequent transplantation. However, a significant proportion of patients who have previously received chemotherapy or radiotherapy...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2017.05.004
更新日期:2017-08-01 00:00:00
abstract::The transcription factor SCL is critically required for establishing hematopoiesis and for proper endothelial development, but not for maintenance of hematopoietic stem cells or endothelial cells in the adult. Conflicting data exists regarding the developmental function of SCL, namely, whether it acts as a master regu...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.07.005
更新日期:2008-12-01 00:00:00
abstract::Bone marrow endothelial cells are likely to play an important role in the homing of hematopoietic progenitor cells. In view of analyzing the interactions between endothelial cells and hematopoietic progenitor cells, we studied several methods of isolating endothelial cells from human bone marrow, including fluorescenc...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract:OBJECTIVE:About one third of patients requiring allogeneic hematopoetic stem cell transplantation (HSCT) would not find a matched sibling or alternative donor. Allogeneic HSCT from matched unrelated and mismatched donors carries an increased risk of graft-vs-host disease (GVHD) and transplant-related mortality (TRM). ...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2008.03.011
更新日期:2008-08-01 00:00:00
abstract::Nasal natural killer-T cell lymphoma (NNKTL) is associated with the Epstein-Barr virus and has distinct histologic features, such as angiocentric and polymorphous lymphoreticular infiltrates that contain too many cell types, including tumor and inflammatory cells. We have shown previously that intercellular adhesion m...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2013.03.009
更新日期:2013-08-01 00:00:00
abstract::An evaluation of the effectiveness of a genetically engineered recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin 3 (IL-3) fusion protein (FP) as a means of delivering cytokine combinations to megakaryocyte (MK) progenitor cells was performed, utilizing a serum-depleted clonal assay syst...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1992-05-01 00:00:00
abstract::The statistical distribution of colony counts in the spleen colony assay was determined in C57BL/6 and C3H mice under varying conditions of the assay procedure. Assay mice were given syngeneic bone marrow cells from normal or irradiated donors. The mice were injected intravenously with marrow cells either immediately ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1977-11-01 00:00:00
abstract:OBJECTIVE:Preservation of hematopoietic stem and progenitor cells from early radiation-induced apoptosis is the rationale for emergency antiapoptotic cytokine therapy (EACK) after radiation accidents. This strategy is based on the combination of stem cell factor + Flt3-ligand + thrombopoietin + interleukin 3 (SFT3). Th...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.04.017
更新日期:2007-08-01 00:00:00
abstract:OBJECTIVES:Macrophage inflammatory protein-1alpha (MIP-1alpha), an osteoclast (OCL) stimulatory factor produced by primary multiple myeloma (MM) cells, increases bone destruction and tumor burden in murine models of MM. Several chemokine receptors (CCR1, CCR5, and CCR9) mediate the effects of MIP-1alpha. In this study,...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.11.015
更新日期:2005-03-01 00:00:00
abstract:OBJECTIVE:Based on previous animal experiments that suggest the plasticity of peripheral blood-derived, CD34(-) stem cell lines, the aim of this study was to isolate CD34(-) stem cell lines from human peripheral blood cells and obtain evidence of their multipotency and plasticity. MATERIALS AND METHODS:Adherent growin...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00865-2
更新日期:2002-08-01 00:00:00
abstract:OBJECTIVE:Umbilical cord blood (CB) provides an alternative source of hematopoietic progenitor cells for transplantation; however, prolonged thrombocytopenia remains a major obstacle due to the low numbers of megakaryocyte progenitor (Mk-prog) cells and their subsequent delayed engraftment. In this study, we improved t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00884-6
更新日期:2002-09-01 00:00:00
abstract::G-banded metaphase chromosomes prepared from 14 male CBA/Ca mice with histologically confirmed myeloid leukemia (ML) were studied in an effort to identify specific chromosomal changes associated with radiation leukemogenesis. The chromosome studies were undertaken as part of a larger investigation of radiation carcino...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-03-01 00:00:00
abstract::Initiation of DNA synthesis by recombinant colony-stimulating factors (CSFs) was assessed in normal human marrow blast cells isolated by expression of CD34 antigen (tritiated thymidine incorporation). Continuous exposure to CSF was required. A mild increase in DNA synthesis was initiated by granulocyte CSF (G-CSF; gre...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-09-01 00:00:00
abstract::The rae28 gene (rae28) is a murine homologue of the Drosophila polyhomeotic gene, which is a member of the Polycomb-group genes. In this study, we examined the role of rae28 in lymphocyte development. Because homozygous rae28-deficient (rae28-/-) mice died in the perinatal period, we examined lymphocyte development by...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00620-2
更新日期:2001-01-01 00:00:00
abstract:OBJECTIVE:Approximately 60% of all anaplastic large-cell lymphomas (ALCL) contain a specific t(2;5)(p23;q35) chromosomal translocation leading to overexpression of NPM-ALK. As the chimeric tyrosine kinase is involved in tumorigenesis and pathogenesis of ALCL, we were interested to inhibit NPM-ALK expression using an ex...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)01084-6
更新日期:2003-03-01 00:00:00
abstract:OBJECTIVE:A multi-step statistical strategy was applied to quantify individual and interactive effects of cytokines on megakaryopoiesis and to determine the concentration of the selected cytokines that optimize ex vivo megakaryocyte (MK) expansion, maturation, and platelet production in stromal- and serum-free conditio...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.06.020
更新日期:2005-10-01 00:00:00
abstract::Colony forming unit (CFU) assays were developed for feline granulocyte-macrophage (CFUGM), early erythroid (day 2 CFUE), and late erythroid (day 7 CFUE) colonies in methylcellulose medium. Feline CFUGM and both day 2 and day 7 CFUE were enhanced by feline macrophage conditioned medium and late CFUE often were intimate...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1981-11-01 00:00:00
abstract:OBJECTIVES:To analyze the consequences of lymphocyte donations on lymphopoiesis in donors having previously undergone hematopoietic stem cell collection for allogeneic stem cell transplantation. METHODS:Repeated analysis of leukocyte subsets in the peripheral blood of 76 hematopoietic stem cell donors undergoing lymph...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.07.021
更新日期:2004-11-01 00:00:00