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 exogenous and an endogenous ribozyme approach. METHODS:We designed five anti-ALK hammerhead ribozymes that were targeted to cleave the ALK proportion of NPM-ALK. The ribozyme with the highest cleavage activity was used as a modified RNA/DNA chimera (RZ1*) for transient transfection and as a self-splicing ribozyme vector (pRZ1) for endogenous expression. Ribozyme performance was tested in 293 cells (cotransfected with NPM-ALK) and in the ALCL cell line Karpas 299 by transient and stable transfection and Western blotting. The half-life time of NPM-ALK was determined by pulse-chase experiments. RESULTS:In vitro cleavage assays demonstrated different catalytic efficiencies depending on the targeted site of the substrate. Constant transfection of Karpas 299 cells with RZ1* for 96 hours did not lead to a significant reduction of NPM-ALK protein, presumably due to the long half-life of NPM-ALK (48 hours). In contrast, NPM-ALK protein expression was almost completely suppressed in transiently transfected 293 cells. Stable transfection of Karpas 299 cells with pRZ1 also resulted in significant reduction of NPM-ALK expression. CONCLUSION:These results suggest that ribozymes targeted against NPM-ALK are able to inhibit expression of this oncogenic kinase efficiently and will be a useful tool to analyze its role in the pathophysiology of ALCL.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Hübinger G,Wehnes E,Xue L,Morris SW,Maurer Udoi
10.1016/s0301-472x(02)01084-6keywords:
subject
Has Abstractpub_date
2003-03-01 00:00:00pages
226-33issue
3eissn
0301-472Xissn
1873-2399pii
S0301472X02010846journal_volume
31pub_type
杂志文章abstract：OBJECTIVE:Podocalyxin expression on Ter119(+) erythroblasts is induced following administration of erythropoietin (Epo) or phenylhydrazine treatment, but is notably absent on committed erythroid progenitors during homeostatic red cell turnover. Following high-dose Epo administration in vivo, podocalyxin surface express...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.09.006
更新日期：2009-01-01 00:00:00
abstract：:Ouabain has been shown to increase the number of clonally derived erythroid stem cells, CFUE and BFUE, from normal murine bone marrow. We report here that digoxin and theophylline also enhance erythroid stem cell colony formation, in the presence of suboptimal concentrations of erythropoietin (Ep) (0.01 IU/ml) in meth...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1982-09-01 00:00:00
abstract：OBJECTIVE:Potent immunosuppressants, such as rapamycin, FK506, and ascomycin, are known to regulate the phosphorylation of proteins. The purpose of this study was to investigate the effects of these immunosuppressants on differentiation of several human myeloid leukemic cell lines. MATERIALS AND METHODS:Human myeloid ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(01)00626-9
更新日期：2001-05-01 00:00:00
abstract：OBJECTIVE:Interaction between hematopoietic cells and stromal cells is important for regulation of hematopoiesis. Numerous soluble and membrane-bound factors directly regulating hematopoiesis have been documented, but little is known about how stromal cell activity is controlled. We previously reported that fetal hepat...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(01)00686-5
更新日期：2001-09-01 00:00:00
abstract：OBJECTIVE:Murine marrow cells are capable of repopulating skeletal muscle fibers. A point of concern has been the "robustness" of such conversions. We have investigated the impact of type of cell delivery, muscle injury, nature of delivered cell, and stem cell mobilizations on marrow-to-muscle conversion. METHODS:We t...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2004.02.007
更新日期：2004-05-01 00:00:00
abstract：:It is becoming increasingly clear that the adeno-associated virus 2 (AAV)-based vector system may prove to be useful for high-efficiency gene transfer in human cells as well as for potential gene therapy in humans. A recombinant AAV vector containing the gene for a human hematopoietic growth factor, granulocyte-macrop...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-11-01 00:00:00
abstract：:As neutropenia is a common side effect of treatment with 2-chlorodeoxyadenosine (2-CdA), we investigated the myelosuppressive action of 2-CdA in Dexter-type human long-term bone marrow cultures (LTBMCs). LTBMCs were incubated with varying doses of 2-CdA (5 to 20 nM/L) during the first week. At 20 and 10 nM/L 2-CdA, we...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-06-01 00:00:00
abstract：:C3H/Km flora-defined mice were used to investigate the effect of exposure to pulsing electromagnetic field (PEMF) after total body x-ray irradiation. Prolonged exposure to PEMF had no effect on normal nonirradiated mice. When mice irradiated with different doses of x-ray (8.5 Gy, 6.8 Gy, and 6.3 Gy) were exposed to PE...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-02-01 00:00:00
abstract：OBJECTIVE:Several requirements need to be fulfilled for clinical use of expanded hematopoietic stem cells (HSCs). Because most cord blood (CB) samples are frozen in single bags and only an aliquot ( approximately 25%) of the blood can be expanded, the thawing and refreezing of samples must be validated in the current E...
journal_title：Experimental hematology
pub_type： 杂志文章,多中心研究
doi：10.1016/j.exphem.2007.08.030
更新日期：2008-02-01 00:00:00
abstract：:Increasing evidence points to endoglin (Eng), an accessory receptor for the transforming growth factor-β superfamily commonly associated with the endothelial lineage, as an important regulator of the hematopoietic lineage. We have shown that lack of Eng results in reduced numbers of primitive erythroid colonies as wel...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2012.06.007
更新日期：2012-10-01 00:00:00
abstract：:Exosomes are virus-size membrane-bound vesicles of endocytic origin present in all body fluids. Plasma of AML patients is significantly enriched in exosomes, which carry a cargo of immunosuppressive molecules and deliver them to recipient immune cells, suppressing their functions. However, whether these exosomes origi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2019.07.005
更新日期：2019-08-01 00:00:00
abstract：:BCR-ABL-negative myeloproliferative neoplasms (MPNs) are driven by JAK-STAT pathway activation, but epigenetic alterations also play an important pathophysiological role. These can be pharmacologically manipulated with histone deacetylase inhibitors (HDACIs), which have proven to be clinically effective in the treatme...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2019.02.002
更新日期：2019-04-01 00:00:00
abstract：:In the present study we investigated the absolute numbers of granulocytic progenitor cells (CFUc) in the spleens of adult normal dogs, their differentiation pattern and also their proliferative state. Between 10 and 40 times as many CFUc were found in the spleens of individual dogs as were present in the total blood v...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-09-01 00:00:00
abstract：OBJECTIVE:Mechanisms of T-cell stimulation by Flt3 ligand (Flt3L) and granulocyte-macrophage colony-stimulating factor (GM-CSF) remain unclear. Herein, we compared the effects of Flt3L and GM-CSF on the expansion of dendritic cells (DC) and T-cell subsets and cytokine expression. METHODS:Naïve and effector/memory T ce...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(01)00722-6
更新日期：2001-10-01 00:00:00
abstract：:Clonality studies can establish the single-cell origin of tumors and thus differentiate clonal malignant and premalignant processes from reactive polyclonal processes. Detection of clonal cells may be based on direct tracking of cell lineage-specific sequences or disease-specific somatic mutations identifying the clon...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2020.01.013
更新日期：2020-03-01 00:00:00
abstract：:Collagen gel was used as a substance for the assay of human granulocyte-macrophage colony-forming units (CFUc). The number of colonies formed in collagen gel was consistently higher than that in a conventional soft-agar system. In six out of eight experiments, the difference was statistically significant. Whole perman...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1984-05-01 00:00:00
abstract：:Bone marrow-derived mast cell precursors form large mast cell colonies in methylcellulose and are designated as L-CFU-Mast. The effect of differentiated mast cells on recruitment and differentiation of L-CFU-Mast was investigated by using genetically mast cell-deficient WBB6F1-W/Wv mice. Giant granules of C57BL/6-bgJ/...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
abstract：OBJECTIVE:To investigate the interaction of imatinib mesylate (IM) with the clinically relevant adenosine triphosphate-binding cassette efflux transporter MDR1 (ABCB1) in cells from patients with chronic myeloid leukemia (CML) and to explore whether inhibition of this transporter would improve IM's efficacy in the elim...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2009.02.006
更新日期：2009-06-01 00:00:00
abstract：:The more mature erythroid progenitor assayable in vitro, the colony-forming unit-erythroid (CFU-E), is normally found in the bone marrow (BM) but is virtually absent from peripheral blood (PB), unlike the more immature progenitor, the burst-forming unit-erythroid (BFU-E). We report on the detection of CFU-E in the PB ...
journal_title：Experimental hematology
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1995-12-01 00:00:00
abstract：:Early hematopoietic progenitor cells adhere to bone marrow stromal cells (BMSCs) mainly through VLA-4/VCAM-1 interactions. However, many adhesion molecules are expressed by these cell types. Cell adhesion molecules not only mediate adhesion; some are also capable of triggering cellular signaling events. These signals ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1997-04-01 00:00:00
abstract：OBJECTIVE:Excessive apoptosis may have a role in the ineffective hematopoiesis and cytopenias observed in myelodysplastic syndromes. The goals of this study were 1) to quantify apoptosis in patients with "early stage" myelodysplasia [including patients with refractory anemia (RA), RA with ringed sideroblasts (RARS), RA...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(00)00179-x
更新日期：2000-07-01 00:00:00
abstract：:After a single pharmacologic dose of estriol (E3) treatment, an increase in number of focal areas of hepatic hemopoiesis was observed in adult mice. When syngeneic bone marrow cells were transfused into E3-treated mice, focal hepatic hemopoiesis was increased further. In a single experiment, using a single cell suspen...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1983-08-01 00:00:00
abstract：:Fourteen patients with chronic granulocytic leukemia received bone marrow grafts from HLA identical siblings. Ten patients were in blast crisis prior to grafting, three were in an accelerated phase of their disease, and one was aplastic secondary to chemotherapy. Prior to transplant all patients were conditioned with ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1978-10-01 00:00:00
abstract：:Cardiovascular diseases (CVDs) remain the leading cause of death worldwide. Many studies have provided evidence that both genetic and environmental factors induce atherosclerosis, leading thus to cardiovascular complications. Atherosclerosis is an inflammatory disease, and aging is strongly associated with the develop...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2019.12.006
更新日期：2020-03-01 00:00:00
abstract：OBJECTIVE:Intravenous (IV) injection is currently the normal method for transplanting hematopoietic cells. However, the problem of seeding efficiency and homing is relevant especially when a limited number of stem cells is available. Intra-bone marrow (IBM) injection of bone marrow cells (BMCs) may overcome this proble...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2004.05.026
更新日期：2004-08-01 00:00:00
abstract：:The megakaryocytopoiesis in rats was studied following a single dose of thio-TEPA to determine the mechanisms for the thrombocytopenia and subsequent recovery. The blood platelet number, platelet production (measured by 35S incorporation into platelets), mean platelet volume, and the number and DNA content of bone mar...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1986-03-01 00:00:00
abstract：OBJECTIVE:Hematopoietic progenitor cells are a promising source for generation of genetically modified dendritic cells. A prerequisite for using these cells in therapeutic approaches is stable vector-mediated transgene expression during and after cell maturation. We investigated the expression of enhanced green fluores...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(01)00778-0
更新日期：2002-02-01 00:00:00
abstract：OBJECTIVE:We previously showed enhanced engraftment of human T cells in the transgenic NonObese Diabetic/severe combined immunodeficient (NOD/scid)-DR1 mice, compared to NOD/scid mice. We now characterize their immunobiology, innate immunity, and intrahepatic neonatal engraftment of cord blood mononuclear cells (CBMNC)...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.05.002
更新日期：2007-08-01 00:00:00
abstract：:The extent of incorporation of bromodeoxyuridine (BrdUrd) into DNA of different types of hematopoietic stem cells assayed in vivo and of progenitor cells assayed in vitro was determined after continuous infusion of BrdUrd into mice for either four or seven days. Cells surviving subsequent exposure to 320 nm ultraviole...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1984-10-01 00:00:00
abstract：:The course of development of graft-versus-host reactions (GVHR) following lethal irradiation was compared in two mouse donor-host combinations disparate at non H-2 loci alone or associated to H-2 complex. The pathogenesis of these reactions was very different (mortality rates faster in the second situation for example...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1981-05-01 00:00:00
