Abstract:
OBJECTIVE:Unresponsiveness to chemotherapy is a major problem in the treatment of leukemia, which can be caused by unresponsiveness of noncycling cells to cell cycle-dependent cytotoxic agents. Targeted toxins consisting of a targeting and activating cytokine (granulocyte-macrophage colony-stimulating factor [GM-CSF]) and diphtheria toxin (DT) can be used to overcome this kind of resistance of leukemic cells. In this study we manipulated the cell cycle and proliferative status of leukemic cells, explored the effect on sensitivity to DT, and determined the ability of DT388GMCSF fusion proteins to activate and subsequently kill leukemic cells. MATERIALS AND METHODS:We used the GM-CSF-dependent myeloid leukemic cell line AML-193 as a model. GM-CSF or granulocyte colony-stimulating factor (G-CSF) was used to manipulate the cell cycle and proliferative state of AML-193 cells. Cell death was quantified by 51Cr release assays. The results obtained in the AML-193 cell line model were confirmed using primary leukemic blasts. RESULTS:Similar to treatment with chemotherapy and immunotherapy, leukemic cells in resting G0 phase were relatively resistant to DT-induced cell death. Synchronized recruitment of leukemic cells into activated phases of the cell cycle by low concentrations of GM-CSF or G-CSF resulted in significant increased DT sensitivity. DT388GMCSF fusion proteins specifically targeted GM-CSF receptor-expressing cells, resulting in recruitment of leukemic cells from G0 phase of the cell cycle and subsequent kill of these cells. CONCLUSION:Leukemic cells in G0 phase, which are resistant to conventional chemotherapy, Fas-induced immunotherapy, and DT alone, can be synchronically activated and subsequently killed by DT388GMCSF fusion proteins.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Jedema I,Barge RM,Frankel AE,Willemze R,Falkenburg JHdoi
10.1016/j.exphem.2003.11.005keywords:
subject
Has Abstractpub_date
2004-02-01 00:00:00pages
188-94issue
2eissn
0301-472Xissn
1873-2399pii
S0301472X03003916journal_volume
32pub_type
杂志文章abstract::The effect of recombinant interleukin 3 (IL-3) on the function of murine resident peritoneal macrophages was investigated. IL-3 enhanced the phagocytosis of Candida pseudotropicalis and Candida albicans and enhanced killing of the former. The enhanced killing is inhibited by scavengers of oxygen radicals, suggesting t...
journal_title:Experimental hematology
pub_type: 杂志文章
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更新日期:1989-09-01 00:00:00
abstract::In the human bone marrow the nuclear enzyme terminal deoxynucleotidyl transferase (TdT) is expressed by cells during early stages of lymphocyte differentiation. In order to investigate a possible regulation of lymphopoiesis at this level of differentiation, the relative frequency and the in vitro 3H-thymidine labeling...
journal_title:Experimental hematology
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abstract:OBJECTIVE:The evolutionarily conserved Kit receptor is vital for function of hematopoietic stem cells (HSC). Kit(W-41) (W-41) and Kit(W-42) (W-42) are single residue changes in the KIT intracellular phosphotransferase domain, while Kit(W-v) (W-v) is a single residue change in the ATP binding domain. This study tests ho...
journal_title:Experimental hematology
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.04.012
更新日期:2008-10-01 00:00:00
abstract::Addition of serum or plasma from many species increased the number and size of neutrophilic granulocyte and macrophage colonies formed in vitro by mouse bone marrow cells after stimulation by a variety of preparations containing colony stimulating factor (CSF). The active factor in serum was heat-labile, non-dialyzabl...
journal_title:Experimental hematology
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更新日期:1975-08-01 00:00:00
abstract::The effects of the inhibition of the cyclooxygenase and lipoxygenase metabolic pathways of arachidonic acid on the postirradiation recovery of hematopoietic functions in mice were investigated. Nordihydroguaiaretic acid (NDGA), an inhibitor of prostaglandin (PG) and leukotriene (LT) production, was given to animals in...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::Cells of the murine interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) factor-dependent line, FDC-P1, express the tyrosine kinase receptor, c-kit. The ligand for c-kit, steel factor (SLF), encoded by the steel (Sl) locus, is produced as both membrane-bound and soluble forms by fibroblast...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-06-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2018.07.001
更新日期:2018-10-01 00:00:00
abstract:OBJECTIVE:Among Philadelphia chromosome-negative myeloproliferative neoplasms (Ph(-) MPN), essential thrombocythemia (ET) and the prefibrotic phase of primary myelofibrosis (PMF) represent two subtypes with considerable overlap. MATERIALS AND METHODS:In this study, histopathological classification of 490 MPN cases was...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.07.005
更新日期:2009-10-01 00:00:00
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journal_title:Experimental hematology
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更新日期:1980-09-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-06-01 00:00:00
abstract::A modified regimen of high-dose cyclophosphamide (CTX) plus cyclosporine (CsA) was adopted for patients with severe or very severe aplastic anemia, and the effectiveness was compared with a regimen of antithymocyte globulin (ATG) plus CsA. A total of 121 patients enrolled in this study received either CTX plus CsA (CT...
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pub_type: 临床试验,杂志文章
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更新日期:2013-04-01 00:00:00
abstract::Deletion of chromosome 13q is believed to be an adverse prognostic marker in patients with multiple myeloma (MM). Interphase fluorescence in situ hybridization (I-FISH) is the method of choice for detection of chromosome 13q deletion (del13q). However, I-FISH has high false-positive rates attributed to a low percentag...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2003.12.001
更新日期:2004-03-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-06-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/s0301-472x(99)00050-8
更新日期:1999-07-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-03-01 00:00:00
abstract::Although three molecular forms of macrophage colony-stimulating factor (M-CSF) have been reported, Western blot analysis of immunoaffinity-purified M-CSF from human blood has shown that the major species of M-CSF in the serum has a molecular weight (MW) of 85 kD. Superose-12 gel filtration chromatography of immunoaffi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2017.07.005
更新日期:2017-11-01 00:00:00
abstract::Imatinib mesylate (IM), a tyrosine kinase inhibitor currently used in chronic myeloid leukemia (CML), may also affect the growth of other cellular systems besides CML cells. Because it has been reported that IM may affect bone tissue remodeling, we evaluated the effects of IM on osteoblastic differentiation of human b...
journal_title:Experimental hematology
pub_type: 杂志文章
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journal_title:Experimental hematology
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doi:
更新日期:1993-11-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.08.028
更新日期:2008-01-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2019.11.007
更新日期:2019-12-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-11-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
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更新日期:2007-03-01 00:00:00
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pub_type: 杂志文章
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