Abstract:
:Granulocyte colony-stimulating factor (G-CSF) is used routinely in the clinical setting to mobilize hematopoietic stem progenitor cells (HSPCs) into the patient's blood for collection and subsequent transplantation. However, a significant proportion of patients who have previously received chemotherapy or radiotherapy and require autologous HSPC transplantation cannot mobilize the minimal threshold of mobilized HSPCs to achieve rapid and successful hematopoietic reconstitution. Although several alternatives to the G-CSF regime have been tested, few are used in the clinical setting. We have shown previously in mice that administration of prolyl 4-hydroxylase domain enzyme (PHD) inhibitors, which stabilize hypoxia-inducible factor (HIF)-1α, synergize with G-CSF in vivo to enhance mouse HSPC mobilization into blood, leading to enhanced engraftment via an HSPC-intrinsic mechanism. To evaluate whether PHD inhibitors could be used to enhance mobilization of human HSPCs, we humanized nonobese, diabetic severe combined immune-deficient Il2rg-/- mice by transplanting them with human umbilical cord blood CD34+ HSPCs and then treating them with G-CSF with and without co-administration of the PHD inhibitor FG-4497. We observed that combination treatment with G-CSF and FG-4497 resulted in significant mobilization of human lineage-negative (Lin-) CD34+ HSPCs and more primitive human Lin-CD34+CD38- HSPCs into blood and spleen, whereas mice treated with G-CSF alone did not mobilize human HSPCs significantly. These results suggest that the PHD inhibitor FG-4497 also increases human HSPC mobilization in a xenograft mouse model, suggesting the possibility of testing PHD inhibitors to boost HSPC mobilization in response to G-CSF in humans.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Nowlan B,Futrega K,Brunck ME,Walkinshaw G,Flippin LE,Doran MR,Levesque JPdoi
10.1016/j.exphem.2017.05.004subject
Has Abstractpub_date
2017-08-01 00:00:00pages
50-55.e6eissn
0301-472Xissn
1873-2399pii
S0301-472X(17)30147-9journal_volume
52pub_type
杂志文章abstract::Normal human peripheral blood mononuclear cells (MNCs), particularly T lymphocytes (T cells), are a rich source of granulocyte-macrophage colony-stimulating factor (GM-CSF). Glucocorticoids are known to inhibit GM-CSF production in in vitro cultures of a human fibroblast cell line and in normal human blood monocytes a...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1998-12-01 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::Acute myeloid leukemia (AML) is a disease with a poor prognosis. It has been demonstrated that AML cells express vascular endothelial growth factor (VEGF) as well as Flt-1 and KDR, resulting in an autocrine pathway for cell survival. PTK787/ZK 222584 is a new oral antiangiogenic molecule that inhibits tyrosine kinase ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.03.001
更新日期:2009-06-01 00:00:00
abstract::Neutropenia is common to both Hermansky-Pudlak syndrome type 2 and canine cyclic hematopoiesis (CH) which are caused by mutations in the AP3B1 gene. The purpose of this study was to determine if pearl mice were neutropenic. Complete blood counts (CBCs) and bone marrow differential counts, colony forming unit (CFU) ass...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2013.05.002
更新日期:2013-10-01 00:00:00
abstract::Radiation damage to femoral hemopoietic stroma in mice was measured 6 weeks after irradiation and reconstitution with syngeneic bone marrow by quantitation of fibroblastic progenitor cells (CFUF), and by assaying hemopoietic progenitors and CFUF numbers in regenerated subcutaneous femur implants. A dose-dependent effe...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1983-10-01 00:00:00
abstract::HIV-derived lentiviral vectors have been used widely to transduce non-dividing cells, such as hematopoietic stem cells (HSCs), in the setting of gene therapy. In this study, we screened lentiviral vectors for their ability to drive expression of the murine MHC class II chaperone, invariant chain (Ii) and a GFP reporte...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2013.07.002
更新日期:2013-11-01 00:00:00
abstract:OBJECTIVE:Resveratrol (3,4',5,-trihydroxystilbene, RV), an ingredient of wine, is an inhibitor of the proliferation-linked enzyme ribonucleotide reductase (RR) and shows a broad spectrum of cytotoxic effects against human cancer cells. In order to enhance these effects, we introduced additional hydroxyl moieties into t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.05.018
更新日期:2006-10-01 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::Certain biological effects exerted by 4-hydroperoxycyclophosphamide and by 2,4-tetrahydrocyclohexylamine (ASTA-Z-7557), utilized in vitro in the therapy of leukemias and lymphomas to eliminate the occult tumor cells in autologous marrow transplantations, were studied in human lymphocytes cultured in vitro. The data sh...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-11-01 00:00:00
abstract:OBJECTIVE:This article evaluates patients with essential thrombocythemia (ET) to determine whether the V617F mutation in the JAK2 gene affects platelet hemostatic and adhesive molecules, platelet-polymorphonuclear leukocyte (PMN) interactions, and PMN-activation characteristics, as well as plasma hypercoagulation marke...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.01.053
更新日期:2007-05-01 00:00:00
abstract:OBJECTIVE:The function of neutrophils as primary mediators of innate immunity depends on the activity of granule proteins and critical components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Expression of their cognate genes is regulated during neutrophil differentiation by a complex netw...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.02.009
更新日期:2008-07-01 00:00:00
abstract::The history of clonal hematopoiesis (CH) research is punctuated by several seminal discoveries that have forged our understanding of cancer development. The clever application of the principle of random X-chromosome inactivation (XCI) in females led to the development of the first test to identify clonal derivation of...
journal_title:Experimental hematology
pub_type: 历史文章,杂志文章,评审
doi:10.1016/j.exphem.2020.01.008
更新日期:2020-03-01 00:00:00
abstract::Between 30 and 40% of the CSF present in agar was depleted after culture for 1 week with 50,000 nucleated murine bone marrow cells. No statistically significant difference could be detected between this depletion and the extent of depletion of CSF when the amount present was halved. There was no evidence that toxic or...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1977-03-01 00:00:00
abstract::Mds1-Evi1 (also known as Prdm3) and Prdm16 are two highly related zinc finger transcription factors that, within the hematopoietic system, are both expressed primarily in hematopoietic stem cells (HSCs). Our laboratory previously found that constitutive Mds1-Evi1 knockout mice are viable, but their HSCs are unable to ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2020.04.010
更新日期:2020-05-01 00:00:00
abstract::Retroviral gene marking has been used successfully in preclinical and clinical transplantation settings. Highly sensitive techniques for vector insertion-site determination, such as linear amplification-mediated polymerase chain reaction (LAM-PCR) in conjunction with next-generation sequencing, have been introduced to...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2012.09.003
更新日期:2013-01-01 00:00:00
abstract::Dtk (Tyro 3/Sky/Rse/Brt/Tif) belongs to a recently recognized subfamily of receptor tyrosine kinases that also includes Ufo (Axl/Ark) and Mer (Eyk). Ligands for Dtk and Ufo have been identified as protein S and the related molecule Gas6, respectively. This study examined expression of Dtk during ontogeny of the hemato...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::Leukemic monoblasts obtained from three children were evaluated for their in vitro physiologic characteristics. These monoblasts were alpha naphthyl acetate esterase positive, exhibited glass adherence, had IgG membrane receptors, phagocytized latex particles with subsequent nitroblue tetrazolium (NBT) reduction, and ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-01-01 00:00:00
abstract:OBJECTIVES:Processing of epigenomic transcriptional information by cell cycle phase G(1) and decision-making at checkpoint G(1)/S are the final organizational steps preceding gene replication in transcriptional reorientation programs (i.e., switches from proliferation to cycle arrest and neoplastic transformation). Fur...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2008.07.009
更新日期:2008-11-01 00:00:00
abstract::Hematopoietic stem cells (HSC) rely on a highly regulated molecular network to balance self-renewal and lineage specification to sustain life-long hematopoiesis. Despite a plethora of studies aimed at identifying molecules governing HSC fate, our current knowledge of the genes responsible is limited. We have found ins...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2016.01.010
更新日期:2016-05-01 00:00:00
abstract::Lentinan, an antitumor polysaccharide, has been assessed for its potential in vivo to augment erythroid progenitor cells and protect them from the cytotoxic effects of antitumor chemotherapeutics. Lentinan augmented the level of burst-forming units-erythroid (BFU-E) and accelerated the recovery of the reduced number o...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-02-01 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:OBJECTIVE:MicroRNAs (miRNAs) are an abundant class of small noncoding RNAs that regulate diverse cellular functions by sequence-specific inhibition of gene expression. We determined miRNA expression profile during erythroid differentiation and putative roles in erythroid differentiation. METHODS:The expression profile...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.03.014
更新日期:2007-07-01 00:00:00
abstract::Interferon α (IFNα) is used clinically to restore polyclonal hematopoiesis in patients with the myeloproliferative neoplasms polycythemia vera and essential thrombocythemia and to improve chemosensitivity in chronic myeloid leukemia patients. However, the mechanisms by which IFNα affects disease-initiating hematopoiet...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2015.05.013
更新日期:2015-10-01 00:00:00
abstract::Fabry disease is a lysosomal storage disorder that is due to a deficiency in alpha-galactosidase A (alpha-gal A). Previously we have shown that a recombinant retrovirus synthesized for the transfer of the human alpha-gal A coding sequence was able to engineer enzymatic correction of the hydrolase deficiency in fibrobl...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(99)00050-8
更新日期:1999-07-01 00:00:00
abstract::Lithium (Li) is a known stimulator of steady-state granulopoiesis, influencing both pluripotential (CFUS) and granulocyte-macrophage committed stem cell (CFUGM) populations. Li has therefore been suggested to be an effective agent to reduce the neutropenia that often is seen after either cytotoxic chemotherapy or radi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1983-07-01 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::The effect of partially purified thrombopoietic stimulatory factor (TSF) on megakaryocytopoiesis was studied using the soft-gel colony-forming assay and a short-term marrow liquid culture system (STLC) and compared to the effects of megakaryocyte colony-stimulating activity present in pokeweed mitogen-stimulated splee...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-09-01 00:00:00
abstract::Our previous studies suggested that a defect in the hemopoietic microenvironment of bone marrow occurred in the anemia of chronic inflammatory disease. We examined the in vivo hemopoietic and marrow stromal cell (MSC) response of shielded marrow to 5000 rad leg-irradiation (5000 rad LI), the in vitro growth of BFUE, C...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-04-01 00:00:00
abstract::To investigate the value of genetic mutations in the pathogenesis and differential diagnosis of hemophagocytic lymphohistiocytosis (HLH), mutations related to blood and immune deficiency genes were analyzed in patients with HLH. Peripheral blood samples from 33 children diagnosed with HLH on the basis of the 2004 diag...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2019.09.024
更新日期:2019-10-01 00:00:00
abstract::A reliable dose-response curve has been established by exposing normal mice to graded doses of exogenous erythropoietin (ESF). In CF1 femal mice, made polycythemic by exposure to reduced air pressure , 59 Fe incorporation in RBC following injections of ESF (ranging from 0.05 to 3.2 IRP-units) varied according to the...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1976-03-01 00:00:00