Abstract:
OBJECTIVE:To investigate 1) the signal transduction pathways affected by heat shock protein 27 (HSP27) expression; and 2) the expression and regulation of HSP27 in acute myeloid leukemia (AML). MATERIALS AND METHODS:RNA interference studies for HSP27 in leukemic TF-1 cells were used to investigate the effects on downstream signal transduction and apoptosis after VP-16 and CD95/Fas treatment. HSP27 expression and activation was investigated in AML blasts through Western blot analysis. RESULTS:RNA interference for HSP27 resulted in a twofold increase in VP-16-induced apoptosis, which was preceded by enhanced p38 and c-Jun phosphorylation and a twofold increased cytochrome c release into the cytoplasm. DAXX co-immunoprecipitated with HSP27, suggesting an inhibitory role of HSP27 in VP-16-mediated activation of the ASK1/p38/JNK pathway. CD95/Fas-induced apoptosis, however, was unaffected by HSP27 siRNA, due to upregulation of HSP27. Although HSP27 was highly expressed and phosphorylated in primitive monocytic AML blasts (M4-M5, 91%, n=11) and undetectable in myeloid blasts (M1-M2, n=5), VP-16-mediated apoptosis correlated moderately with HSP27 expression. This is likely due to the co-expression of p21Waf1/Cip1, which is in the majority of the monocytic AML M4-M5 blasts constitutively localized in the cytoplasm. Overexpression of cytoplasmic p21 inhibited the enhanced p38 phosphorylation after HSP27 RNAi, suggesting a predominant anti-apoptotic role of p21 over HSP27. CONCLUSION:1) HSP27 inhibits VP-16-mediated phosphorylation of p38 and c-Jun, cytochrome c release, and subsequent apoptosis; 2) HSP27 is expressed and activated in monocytic AML blasts; 3) cytoplasmic expression of p21 compensates for the lack of HSP27.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Schepers H,Geugien M,van der Toorn M,Bryantsev AL,Kampinga HH,Eggen BJ,Vellenga Edoi
10.1016/j.exphem.2005.03.009keywords:
subject
Has Abstractpub_date
2005-06-01 00:00:00pages
660-70issue
6eissn
0301-472Xissn
1873-2399pii
S0301-472X(05)00133-5journal_volume
33pub_type
杂志文章abstract::Assessment of donor chimerism is becoming increasingly important in patients undergoing reduced-intensity conditioning (RIC) allogeneic bone marrow transplants, due to the possibility of mixed chimeras. This regimen has been used successfully for patients with leukemia and genetic disorders with donor chimerism occurr...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.05.028
更新日期:2004-09-01 00:00:00
abstract::As hematopoietic stem and progenitor cells have a low mitotic index, we have quantitated the impact of cytokine combinations on cell cycling of CD34+ cells and, using VSV-G pseudotyped retroviral vectors, correlated our findings with ex vivo gene transfer. We tested nine different combinations of cytokines for inducti...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract:OBJECTIVE:New nonmyeloablative strategies to improve acceptance of mismatched bone marrow (BM) may compensate for the inadequate supply of compatible grafts. Recently we proposed to facilitate engraftment of mismatched BM by selective depletion of activated donor-reactive host cells with cyclophosphamide (CY). Here we ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.07.017
更新日期:2004-11-01 00:00:00
abstract::Germinal center-associated nuclear protein (GANP) is a unique and multifunctional protein that plays a critical role in cell biology, neurodegenerative disorders, immunohematology, and oncogenesis. GANP is an orthologue of Saccharomyces Sac3, one of the components of the transcription export 2 (TREX-2) complex and a m...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2020.08.007
更新日期:2020-10-01 00:00:00
abstract::We have studied the in vivo spleen colony-forming ability and marrow repopulating ability of murine bone marrow cells differing in mitochondrial activity. Following centrifugal elutriation the cells were sorted on the basis of rhodamine-123 fluorescence intensity within a predetermined light scatter window. It is show...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-03-01 00:00:00
abstract:OBJECTIVE:A marker for hematopoietic stem cells (HSCs) of pigs, which are considered to be the most suitable donors for clinical xenotransplantation, has not yet been identified. In this study, we examined the HSC activity of porcine c-kit+ bone marrow cells (BMCs). METHODS:The HSC activity of porcine c-kit+ BMCs was ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(03)00197-8
更新日期:2003-09-01 00:00:00
abstract::The development of pluripotential hematopoietic stem cells (PHSC) requires the continuous support provided by the bone tissue and bone marrow (BM) stromal cells. The basic rule of spatial and temporal organization of the distinct stromal cells and differentiating hematopoietic cells in the course of development, regen...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00
abstract:OBJECTIVE:To assess the contribution of bone marrow (BM)-derived endothelial progenitor cells (EPCs) to the neovascularisation of cutaneous incisional wounds. METHODS:Lethally irradiated C57Bl/6 mice were transplanted with BM mononuclear cells from Tie2/lacZ mice, which constitutively overexpressed beta-galactosidase ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.10.016
更新日期:2007-03-01 00:00:00
abstract::Together, interleukin-1 alpha (IL-1 alpha) and IL-1 beta primed human neutrophils for enhanced release of superoxide (O2-) stimulated by chemotactic peptide, chemokine, and plant lectin, and alone, each triggered O2- release in a dose-dependent manner. The maximal priming and triggering effect was obtained by high con...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-07-01 00:00:00
abstract:OBJECTIVE:Bone marrow contains a subset of stem cells that give rise to nonhematopoietic lineages. These nonhematopoietic stem cells appear heterogeneous and contain cells committed to mesenchymal and endothelial lineages, as well as more primitive multipotential cells resembling progenitors of germ cells and very smal...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.05.014
更新日期:2009-09-01 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:OBJECTIVE:Delayed platelet recovery post-cord blood (CB) transplantation might be due to CB characteristics: low maturity of stem cell compartment, poor production of CD34+/CD41+ cells when induced to differentiate along the megakaryocytic (MK) lineage, retention of a low ploidy in the expanded MKs. Ex vivo expansion o...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.09.006
更新日期:2008-02-01 00:00:00
abstract::Granulocyte colony-stimulating factor (G-CSF) has proven effective in the prophylaxis of chemotherapy-induced neutropenia and as a mobilizer of peripheral blood progenitor cells. The longevity of G-CSF action is limited by its removal from the body by two mechanisms. The first is thought to be mediated via receptors (...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(99)00112-5
更新日期:1999-12-01 00:00:00
abstract::Induced pluripotent stem cells (iPS) derived from disease cells are expected to provide a new experimental material, especially for diseases from which samples are difficult to obtain. In this study, we generated iPS from samples from patients with primary and secondary myelofibrosis. The primary myelofibrosis cells h...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2014.03.010
更新日期:2014-09-01 00:00:00
abstract:OBJECTIVE:The aim of this study was the preclinical evaluation of imatinib mesylate (Gleevec, formerly STI571) in conjunction with arsenic trioxide (As2O3, Trisenox) for the treatment of chronic myelogenous leukemia (CML). MATERIALS AND METHODS:Tetrazolium-based cell line proliferation assays (MTT assays) were perform...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00836-6
更新日期:2002-07-01 00:00:00
abstract::Myelodysplastic syndromes (MDS) are clonal stem cell diseases of the bone marrow characterized by abnormalities in maturation of hematopoietic cells of all lineages. MDS patients frequently have lower lipids and high rates of apoptosis and p53 (TP53) expression. An association between the reduced lipids in MDS and the...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2012.02.003
更新日期:2012-07-01 00:00:00
abstract:OBJECTIVE:Recruitment of endothelial progenitor cells to the sites of ischemia has recently been suggested as a mechanism of tissue repair. Here we address the hypothesis that the hypoxia-inducible full-length endothelial-monocyte-activating polypeptide II (EMAP II) provides a mechanism to recruit late outgrowth highly...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.05.021
更新日期:2006-08-01 00:00:00
abstract::Radiation therapy is used as total body treatment in preparation of the acute myelogenous leukemia (AML) patient for bone marrow transplantation. Many AML patients will have residual leukemia cells at the time of total body irradiation (TBI). In the present study, the effect of TBI on leukemic myeloid cells was compar...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1979-01-01 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::Overexpression of immune-related genes is widely reported in myelodysplastic syndromes (MDSs), and chronic immune stimulation increases the risk for developing MDS. Aberrant innate immune activation, such as that caused by increased toll-like receptor (TLR) signaling, in MDS can contribute to systemic effects on hemat...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2015.05.016
更新日期:2015-08-01 00:00:00
abstract::The tumor suppressor p53 is thought to play a role in megakaryocyte (MK) development. To assess the influence of the p53 regulatory pathway further, we studied the effect of RG7112, a small molecule MDM2 antagonist that activates p53 by preventing its interaction with MDM2, on normal megakaryocytopoiesis and platelet ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2013.11.012
更新日期:2014-02-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00962-1
更新日期:2002-12-01 00:00:00
abstract::Iron, an essential nutrient for cellular growth and proliferation, enters cells via clathrin-mediated endocytosis. The clathrin assembly lymphoid myeloid (CALM) protein plays an essential role in the cellular import of iron by clathrin-mediated endocytosis. CALM-AF10 leukemias harbor a single copy of the normal CALM g...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2014.08.004
更新日期:2014-12-01 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...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2013.01.001
更新日期:2013-04-01 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::The aim of this work was to monitor the functional and phenotypic variations of natural killer (NK) cells in seven children with stage IV neuroblastoma (NB) treated with recurrent 5-day cycles of interleukin-2 (IL-2) at a dose of 18 x 10(6) IU/m2/d by continuous intravenous infusion. All patients who entered the study...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-12-01 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::We performed the present study to define the in vitro hemopoietic activity of murine recombinant (r) granulocyte colony-stimulating factor (G-CSF) using murine hemopoietic culture systems of normal bone marrow cells, fetal liver cells, and spleen cells of 5-fluorouracil (FU)-treated mice. Recombinant G-CSF supported o...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-10-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to develop an animal model for human acute lymphoblastic leukemia (ALL) in which the kinetics and characteristics of leukemia can be sequentially monitored in individual mice. MATERIALS AND METHODS:NOD/SCID mice were inoculated intravenously with primary ALL. Progression of leukemia...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00669-x
更新日期:2001-03-01 00:00:00
abstract::Previous studies in animal models have suggested that bone marrow-derived interleukin-2 (IL-2) activated natural killer (A-NK*) cells can be used to eliminate residual leukemic cells both in vivo and in vitro. As part of initial studies to develop a clinical protocol to exploit this phenomenon in combination with cult...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-08-01 00:00:00