Abstract:
:Stem cell factor (SCF), also termed mast cell growth factor or c-kit ligand, plays a central role in the regulation of hematopoiesis and maintenance of viability of hematopoietic cells. We used a new murine monoclonal antibody (MAb) specific for canine SCF to further dissect the role of SCF in vitro and in vivo. This neutralizing MAb, RG7.6 (IgG1), recognizes the soluble form as well as the membrane-bound form of SCF on marrow-derived stromal cells. Treatment of long-term bone marrow cultures (LTMC) with RG7.6 suppressed or stimulated the production of CFU-GM, depending on the MAb concentration and the time of addition to cultures. At concentrations of 0.1-10 micrograms/ml given on the day of recharge of the LTMC, RG7.6 resulted in sustained suppression of CFU-GM grown from nonadherent cells. In contrast, higher doses of RG7.6 (20-100 micrograms/ml) led to a two- to threefold increase in CFU-GM formation from nonadherent cells after 3 days of RG7.6 exposure; after longer RG7.6 exposure there was a rapid decline in the number of CFU-GM. The early increase of CFU-GM was even more distinct when RG7.6 addition to LTMCs was delayed until 1 day before cells were plated for the CFU-GM assay. The early increase of CFU-GMs in the presence of high-dose RG7.6 was mimicked by the addition of granulocyte colony-stimulating factor (G-CSF) to cultures containing suboptimal concentrations of RG7.6, suggesting the possibility that the "positive" response to high-dose RG7.6 was due to an overriding effect of other growth factors, e.g., G-CSF. In stromal cells expressing the membrane-bound form of SCF, the presence of MAb RG7.6, even at low concentrations, interfered with thymidine uptake and proliferation. RG7.6 was also tested in vivo. RG7.6 was given intravenously immediately (days 0-4) after total body irradiation and autologous bone marrow transplantation, and granulocyte counts were followed. The post-irradiation nadir of peripheral blood granulocytes was indistinguishable from controls at low doses of RG7.6 but became more shallow as higher doses of RG7.6 were infused, again suggesting a positive effect on granulocyte differentiation. Thus, the SCF-specific MAb appears to interfere with both stromal and hematopoietic cell function. While only inhibition was observed at lower concentrations, a transient increase in granulocyte production was seen at higher MAb concentrations.
journal_name
Ann Hematoljournal_title
Annals of hematologyauthors
Huss R,Hong DS,Beckham C,Storb R,Broudy VC,Deeg HJdoi
10.1007/s002770050168subject
Has Abstractpub_date
1996-04-01 00:00:00pages
253-9issue
4eissn
0939-5555issn
1432-0584journal_volume
72pub_type
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journal_title:Annals of hematology
pub_type: 临床试验,杂志文章
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journal_title:Annals of hematology
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更新日期:2012-10-01 00:00:00
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journal_title:Annals of hematology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00277-016-2638-6
更新日期:2016-05-01 00:00:00
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pub_type: 杂志文章,多中心研究
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journal_title:Annals of hematology
pub_type: 杂志文章
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更新日期:2018-06-01 00:00:00
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pub_type: 临床试验,杂志文章
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journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-020-04000-x
更新日期:2020-07-01 00:00:00
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journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-003-0716-z
更新日期:2003-10-01 00:00:00
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journal_title:Annals of hematology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00277-016-2758-z
更新日期:2016-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1007/s00277-008-0643-0
更新日期:2009-06-01 00:00:00
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journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-012-1470-x
更新日期:2012-09-01 00:00:00
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journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-008-0598-1
更新日期:2009-06-01 00:00:00
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journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-004-0952-x
更新日期:2005-02-01 00:00:00
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journal_title:Annals of hematology
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journal_title:Annals of hematology
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journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-016-2672-4
更新日期:2016-06-01 00:00:00
abstract::Lower dosage of total body irradiation (TBI) and chemotherapy in reduced-intensity conditioning (RIC) regimens prior to allogeneic stem cell transplantation have reduced the toxicity of the conditioning and non-relapse mortality. The FLAMSA-RIC protocol for high-risk patients with acute myeloid leukemia (AML) and myel...
journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/s00277-011-1253-9
更新日期:2012-01-01 00:00:00
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journal_title:Annals of hematology
pub_type: 杂志文章
doi:10.1007/BF01714904
更新日期:1991-02-01 00:00:00
abstract::This retrospective single-center study compared thromboembolic and hemorrhagic complications, survival and causes of death in a cohort of 102 consecutive patients with myeloproliferative disorders (MPD). We included 17 patients with essential thrombocythemia (ET), 59 with polycythemia vera (PV), and 26 with osteomyelo...
journal_title:Annals of hematology
pub_type: 杂志文章
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更新日期:2000-06-01 00:00:00
abstract:PURPOSE:To determine whether, after very intensive induction and consolidation therapy in childhood AML, further maintenance therapy (MT) confers any advantage. PATIENTS AND METHODS:Three hundred-nine children with previously untreated AML were registered in the LAME 89/91 protocol. This three-cycle intensive regimen ...
journal_title:Annals of hematology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2004-01-01 00:00:00
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journal_title:Annals of hematology
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更新日期:2008-11-01 00:00:00
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journal_title:Annals of hematology
pub_type: 杂志文章,meta分析
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更新日期:2015-06-01 00:00:00
abstract::This study outlines trends in quality of delivered non-Hodgkin's lymphoma (NHL) care in the Netherlands between 2007 and 2011 and to what extend this was influenced by the national Visible Care program, which aimed at increasing transparency by providing insight into the quality of healthcare. We analyzed data collect...
journal_title:Annals of hematology
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2015-07-01 00:00:00
abstract::Photodynamic virus inactivation of human fresh plasma mediated by visible light in the presence of the phenothiazine dyes methylene blue or toluidine blue was investigated to determine whether it influences functional, structural, and immunological properties of plasma proteins. The activities of the coagulation facto...
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pub_type: 杂志文章
doi:10.1007/BF01703949
更新日期:1992-11-01 00:00:00