Abstract：
OBJECTIVE:Morbidity and mortality occurring in patients with multiple myeloma, AL amyloidosis, and light chain deposition disease can result from the pathologic deposition of monoclonal immunoglobulin light chains (LCs) in kidneys and other organs. To reduce synthesis of such components, therapy for these disorders typically has involved antiplasma cell agents; however, this approach is not always effective and can have adverse consequences. We have investigated another means to achieve this objective; namely, RNA interference. MATERIALS AND METHODS:SP2/O mouse myeloma cells were stably transfected with a construct encoding a λ6 LC (Wil) under control of the cytomegalovirus promoter, while λ2-producing myeloma cell line RPMI 8226 was purchased from the American Type Culture Collection (Manassas, VA, USA). Both were treated with small interfering RNA directed specifically to the V, J, or C portions of the molecules and then analyzed by enzyme-linked immunosorbent assay, flow cytometry, and real-time polymerase chain reaction. RESULTS:Transfected cells were found to constitutively express detectable quantities of messenger RNA and protein Wil and, after exposure to small interfering RNAs, an ∼ 40% reduction in messenger RNA and LC production was evidenced at 48 hours. An even greater effect was seen with the 8226 cells. CONCLUSIONS:Our results have shown that RNA interference can markedly reduce LC synthesis and provide the basis for testing the therapeutic potential of this strategy using in vivo experimental models of multiple myeloma.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Phipps JE,Kestler DP,Foster JS,Kennel SJ,Donnell R,Weiss DT,Solomon A,Wall JSdoi
10.1016/j.exphem.2010.07.001subject
Has Abstractpub_date
2010-11-01 00:00:00pages
1006-13issue
11eissn
0301-472Xissn
1873-2399pii
S0301-472X(10)00282-1journal_volume
38pub_type
杂志文章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...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.06.012
更新日期：2008-11-01 00:00:00
abstract：:We previously reported an in vitro bioassay permissive to eosinophil production from naive mouse bone marrow cells. Based on cytosmear analysis, recombinant murine (rm) interleukin (IL)-3 combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) provided better quantitative cellular yields compared with ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1998-06-01 00:00:00
abstract：OBJECTIVE:To test function of hematopoietic stem cells (HSCs) in vivo in C57BL/6 (B6) and Trp53-deficient (Trp53 null) mice by using two HSC enrichment schemes. MATERIALS AND METHODS:Bone marrow (BM) Lin-CD41-CD48-CD150+ (signaling lymphocyte activation molecules [SLAM]), Lin-CD41-CD48-CD150- (SLAM-) and Lin-Sca1+CD11...
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：:Adult hematological malignancies, such as acute myeloid leukemia, are thought to arise through the gradual acquisition of oncogenic mutations within long-lived hematopoietic stem cells (HSCs). Genomic analysis of peripheral blood DNA has recently identified leukemia-associated genetic mutations within otherwise health...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2019.08.004
更新日期：2019-09-01 00:00:00
abstract：:In a selective culture system, the in vitro generation of terminal deoxynucleotidyl transferase positive (TdT+) B cell progenitors from rat, mouse, and human bone marrow (BM) is characterized by initial lymphoid colonization of a mouse BM feeder layer. In the present study, four sequentially appearing subsets of B cel...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1994-11-01 00:00:00
abstract：OBJECTIVE:Our previous study has shown that granulocyte-macrophage colony-stimulating factor (GM-CSF) gene/silica nanoparticles have a leukocytosis effect in normal dogs. Therefore, this study was conducted to determine whether treatment of canine GM-CSF gene/silica nanoparticles has preventive or therapeutic effects i...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.04.002
更新日期：2008-09-01 00:00:00
abstract：OBJECTIVE:Use of a trifunctional bispecific antibody (trAb) given concomitantly with allogeneic cell therapy to achieve an anti tumor effect without graft-vs-host disease (GVHD). MATERIALS AND METHODS:A trAb-directed against murine CD3 and human epithelial cell adhesion molecule (EpCAM) (BiLu), was given alone or conc...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.03.005
更新日期：2008-08-01 00:00:00
abstract：:The kinetics of cell turnover for myeloid/monocyte cells that form colonies in agar (GM-CFC) were measured through the progressive increase in their sensitivity to 313-nm light during a period of cell labeling with BrdCyd. Two components of cell killing with distinctly separate labeling kinetics revealed both the pres...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1985-07-01 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
abstract：OBJECTIVE:The primary objective of this study was to identify and clone the first nonmammalian thrombopoietin (TPO), chicken TPO, and its receptor c-Mpl for the purpose of characterizing their activities both in vitro and in vivo. MATERIALS AND METHODS:Chicken TPO was cloned using the methods of reverse transcriptase ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.12.001
更新日期：2008-04-01 00:00:00
abstract：OBJECTIVE:T lymphocytes can be activated by soluble factors such as cytokines or through direct cell-cell interactions. Although cytokine receptors are known to signal through STAT family transcription factors, the mechanisms by which other cell-surface molecules, such as CD2, transduce signals is unclear. The goal of ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(00)00652-4
更新日期：2001-02-01 00:00:00
abstract：OBJECTIVE:Hemopoiesis is regulated by cytokines with positive or negative effects on proliferation of lineage-committed or multipotent hemopoietic stem cells. We have investigated the roles of interleukin-6 and other gp130-dependent ligands on the proliferation of macrophage-lineage hemopoietic progenitor cells. METHO...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(00)00512-9
更新日期：2000-10-01 00:00:00
abstract：:To help establish an effective gene therapy protocol for patients with congenital metabolic diseases, we evaluated retrovirus-mediated transduction and long-term (LT) expression of the NeoR gene in cryopreserved and thawed CD34+ cells purified from granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blo...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1997-08-01 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
abstract：OBJECTIVE:The tumor suppressor p15Ink4b (Ink4b) is a cell-cycle inhibitor that is inactivated in a high percentage of acute myeloid leukemia and myeloid dysplasia syndrome cases. Despite this, the role of Ink4b in hematopoiesis remains unclear. Here we examined the role of Ink4b in blood cell formation using Ink4b-defi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.11.005
更新日期：2007-03-01 00:00:00
abstract：:Mice with the nu mutation have been shown to have a reduced incidence of spleen colony-forming units (CFU-S), with a higher variability between individual mice compared to +/+ mice. The presence of these defects also in nu/+ mice indicates that this mutation is a codominant trait and that the hematopoietic changes may...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
abstract：:Type IV nuclear bodies are classified as true intranuclear inclusions that ultrastructurally contain numerous densely packed 20- to 30-nm osmiophilic granules surrounded by a microfibrillar cortex. In the present study, we have found statistically significant ultrastructural differences in the frequency and size of ty...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1987-02-01 00:00:00
abstract：:Cancer stem cells (CSCs), including leukemia stem cells (LSCs), exhibit self-renewal capacity and differentiation potential and have the capacity to maintain or renew and propagate a tumor/leukemia. The initial isolation of CSCs/LSCs was in adult myelogenous leukemia, although more recently, the existence of CSCs in a...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2017.04.010
更新日期：2017-08-01 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：OBJECTIVE:Hematopoietic stem and progenitor cells normally reside in the bone marrow but can be mobilized into the peripheral blood following treatment with granulocyte colony-stimulating factor (G-CSF) or myelosuppressive chemotherapy. Although the number of transplants performed with mobilized blood currently exceeds...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00788-9
更新日期：2002-05-01 00:00:00
abstract：OBJECTIVE:The significant role of direct contact between hematopoietic progenitor cells (HPC) and the cellular microenvironment for maintaining "stemness" has been demonstrated. Human mesenchymal stem cell (MSC) feeder layers represent a surrogate model for this interaction. Specific adhesion molecules are responsible ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.10.003
更新日期：2007-02-01 00:00:00
abstract：:After initially successful chemotherapy, relapse frequently jeopardizes the outcome of patients with acute leukemia. Because of their adverse characteristics of self-renewal and dormancy, leukemia stem cells have been hypothesized to play a critical role in resistance to antiproliferative chemotherapy and the developm...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2018.09.006
更新日期：2019-01-01 00:00:00
abstract：:Benign constitutional neutropenia (BCN) is an asymptomatic condition characterized by mild chronic neutropenia in patients with no history of recurrent infections. Most patients are referred for further testing, increasing health care costs. We present an alternative form of assessment of individuals with BCN based on...
journal_title：Experimental hematology
pub_type： 临床试验,杂志文章
doi：10.1016/j.exphem.2018.10.007
更新日期：2019-01-01 00:00:00
abstract：:Hematopoietic stem/progenitor cells (HSPCs) play important roles in fighting systemic infection as they supply immune cells in a demand-adapted manner. Various mechanisms govern HSPC responses to infection, including cytokine signaling, niche function, and direct sensing of pathogen-derived molecules by HSPCs themselv...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2015.11.008
更新日期：2016-02-01 00:00:00
abstract：:Cholinergic toxicity of organophosphate insecticides is regarded as the principal health hazard associated with both human and animal exposures. Recent studies indicate that these pesticides may have important effects on both the immune and hematopoietic systems. In the present study, human bone marrow cells were expo...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1987-12-01 00:00:00
abstract：:We have investigated the effect of hematopoietic cytokines on the survival of severe combined immune-deficient (SCID) mice that received a high dose of radiation. In this study, female SCID mice were irradiated at doses ranging from 500 to 600 cGy and then transplanted with 2 x 10(6) male Balb/c marrow cells. Groups o...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1994-02-01 00:00:00
abstract：OBJECTIVE:The purpose of this study was to investigate the effects of interleukin-2 (IL-2) gene-transduced hematopoietic progenitor cells or cytotoxic function and systemic toxicity following syngeneic bone marrow transplantation. MATERIAL AND METHODS:Marrow of 5-fluorouracil pretreated donor mice were transfected wit...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(00)00487-2
更新日期：2000-08-01 00:00:00
abstract：:We compared the effects of recombinant (r) tumor necrosis factor (TNF) and lymphotoxin (rLT) on in vitro colony formation by erythroid, multipotential and granulocyte, monocyte (CFU-GM) precursor cells. Recombinant granulocyte, macrophage-colony stimulating factor and bone marrow preparations enriched for hematopoieti...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-02-01 00:00:00
abstract：:Initially described as an endogenous inhibitor of proteases, the tissue inhibitor of metalloproteinases 1 (TIMP-1) also displays cytokine-like functions. TIMP-1 is a soluble protein whose levels are increased under inflammatory conditions. We recently found that TIMP-1(-/-) mice have decreased bone marrow (BM) cellula...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2015.07.003
更新日期：2015-11-01 00:00:00
abstract：:The processing of inflammatory signals occurs through a variety of mechanisms; the recent descriptions of the tethered ligand receptor for thrombin (JA Hoxie et al., J Biol Chem 268:13756, and TK Vu et al., Cell 64:1057) provide a novel route and mechanism for cellular activation after inflammation and thrombosis. Usi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1996-07-01 00:00:00
