Abstract：
OBJECTIVE:We have previously shown that Flt3 ligand (FL)/Flt3 signaling regulates hematopoietic cell migration by modulating the SDF1alpha/CXCR4 signaling pathway. Herein, we evaluated whether a functional interaction between SDF1alpha/CXCR4 signaling and internal tandem duplication (ITD) of Flt3 regulates aberrant hematopoietic survival. We also investigated molecular mechanisms responsible for enhanced migration to SDF1alpha as a result of ITD-Flt3 expression and whether ITD-Flt3 regulates hematopoietic cell trafficking. METHODS:Hematopoietic progenitor cell survival was determined using marrow cells retrovirally expressing ITD-Flt3 and stimulated with SDF1alpha. Migration, to SDF1alpha adhesion to vascular cell adhesion molecule-1, and in vivo homing were determined using Ba/F3 cells expressing ITD-Flt3 and transfected with dominant negative (DN) H-Ras. RESULTS:Addition of SDF1alpha significantly increased growth factor-independent proliferation of colony-forming unit granulocyte-macrophage induced by ITD-Flt3. Although a negative gradient of SDF1alpha inhibited migration regardless of the stimulation, a positive gradient of FL or ITD-Flt3 significantly increased cell migration even in the presence of a negative SDF1alpha gradient. Enhanced migration induced by ITD-Flt3 was inhibited by DN-H-Ras, whereas overexpression of a constitutive active form of H-Ras in wild-type Flt3-Ba/F3 cells significantly elevated migration to SDF1alpha. Despite enhanced migration to SDF1alpha, preincubation with FL or ITD-Flt3 overexpression significantly reduced homing of primary mouse bone marrow cells or Ba/F3 cells to bone marrow that was associated with significant reduction in adhesion to vascular cell adhesion molecule-1 and VLA4 expression. CONCLUSION:Our results suggest that functional interactions between Flt3 and SDF1alpha/CXCR4 regulate oncogenic proliferation and migration of hematopoietic cells, which is mediated by Ras, and that Flt3 signaling regulates hematopoietic cell trafficking in vivo.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Fukuda S,Pelus LMdoi
10.1016/j.exphem.2006.04.001subject
Has Abstractpub_date
2006-08-01 00:00:00pages
1041-51issue
8eissn
0301-472Xissn
1873-2399pii
S0301-472X(06)00239-6journal_volume
34pub_type
杂志文章abstract：:Bone marrow cell responses to therapeutic doses of cis-diamminedichloroplatinum (II) (Cis-Pt) were evaluated in female C57B1/6 mice by determining bone marrow cellularity and content of transplantable colony forming units (CFUS) after treatment. Although limitation on the dosage of Cis-Pt is generally considered to be...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1981-03-01 00:00:00
abstract：:We have utilized two well-characterized human leukemia/lymphoma (LL) cell lines, UTMB-460 and CEM, to determine the role of integrin very late antigen-alpha 4 beta 1 (VLA-4) and its ligand vascular cell adhesion molecule-1 (VCAM-1) in the adherence of the LL cells to marrow stromal cells (MSC). Both these LL cell line...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-03-01 00:00:00
abstract：:Acute disseminated intravascular coagulation (DIC) is a life-threatening condition that may be encountered in many situations, especially in cases of shock with uncontrollable hemorrhage. Anisodamine, an alkaloid extracted from a Chinese herb, is well known for its dramatic therapeutic effect on DIC. Sixty male rabbit...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1987-01-01 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：:Hematopoiesis in continuous bone marrow culture is dependent upon close-range interaction between hematopoietic cells and marrow-derived adherent cells. The latter have been shown to include a significant proportion of fibroblastic elements, synthesizing the attachment protein fibronectin. The role of fibronectin in c...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1983-02-01 00:00:00
abstract：:Details are given of response and toxicity after high dose chemotherapy followed by autologous bone marrow infusion. High dose nitrosurea therapy (600-1000 mg/m2 BCNU) was predominantly associated with hematopoietic toxicity but recovery was within 4-5 weeks after BCNU therapy. High dose combination chemotherapy using...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1979-01-01 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：:We have assessed the potential use of the mononuclear cell (MNC) content as the sole assessment of graft quality in 35 patients receiving BEAM (carmustine, etoposide, cytosine arabinoside, melphalan) chemotherapy and autologous peripheral blood progenitor cell (PBPC) transplantation for malignant lymphoma. PBPCs were ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-12-01 00:00:00
abstract：:Persistent reductions in the femoral content of hemopoietic colony-forming cells (CFU-S and GM-CFC) were observed after four doses of irradiation, delivered with three weeks between doses. In general, the reductions were dose dependent, and similar reductions were produced by single doses and repeated doses using the ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1986-03-01 00:00:00
abstract：OBJECTIVE:Thrombopoietin stimulates megakaryopoiesis and platelet production by binding to its receptor, Mpl, on hematopoietic progenitor cells. Previously, a murine VB22B minibody for Mpl was shown to stimulate megakaryocyte colony formation in vitro and increase the platelet count in cynomolgus monkeys. In this study...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2011.05.001
更新日期：2011-08-01 00:00:00
abstract：OBJECTIVE:A multi-step statistical strategy was applied to quantify individual and interactive effects of cytokines on megakaryopoiesis and to determine the concentration of the selected cytokines that optimize ex vivo megakaryocyte (MK) expansion, maturation, and platelet production in stromal- and serum-free conditio...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2005.06.020
更新日期：2005-10-01 00:00:00
abstract：UNLABELLED:In this paper we describe an experimental model for ex vivo purging of contaminating tumor cells from peripheral blood stem cell (PBSC) collections obtained from patients with acute myeloblastic leukemia (AML). We studied the combination of the alkylating agent nitrogen mustard (NM; concentrations ranging fr...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1997-11-01 00:00:00
abstract：:Malignant osteopetrosis is a disorder characterized by a deficiency in osteoclast number or function. In one animal model of osteopetrosis, the op/op mouse, macrophage colony-stimulating factor (M-CSF) is absent, and the administration of M-CSF corrects the defects. We evaluated the serum of 13 patients with malignant...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1992-01-01 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：:The microenvironment (niche) governs the fate of stem cells (SCs) by balancing self-renewal and differentiation. Increasing evidence indicates that the tumor niche plays an active role in cancer, but its important properties for tumor initiation progression and resistance remain to be identified. Clinical data show th...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2018.02.005
更新日期：2018-05-01 00:00:00
abstract：:During chronic hypoxia, the number of splenic erythroid progenitor cells in mice, particularly CFU-E, increased dramatically but transiently. Since all three classes of erythroid progenitors in the femoral bone marrow were suppressed, a large part of this increase might be attributed to migration of CFU-E and/or their...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-01-01 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：: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：: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：:Peripheral blood lymphocytes obtained at 24-30 months after birth from a male with X-linked severe combined immune deficiency maintained in a gnotobiotic environment were characterized by T and B cell surface markers. A high proportion (55-80 percent) of circulating lymphocytes bore surface IgM as detected by direct i...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1976-01-01 00:00:00
abstract：:The fate of hematopoietic progenitor cells (HPCs) in the bone marrow (BM) microenvironment is determined by two different interactions: 1) they adhere (via integrins) to both extracellular matrix molecules and BM stromal cells; and 2) stromal cells produce cytokines that influence their survival, proliferation, differ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1998-08-01 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：:Similarly to other tissues, the bone marrow contains subsets of resident tissue macrophages, which are essential to maintain bone formation, functional hematopoietic stem cell (HSC) niches, and erythropoiesis. Pharmacologic doses of granulocyte colony-stimulating factor (G-CSF) mobilize HSC in part by interfering with...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2014.03.009
更新日期：2014-07-01 00:00:00
abstract：:Drug resistance remains a serious problem in leukemia therapy. Among newly developed nucleoside antimetabolites, clofarabine has broad cytotoxic activity showing therapeutic promise and is currently approved for relapsed acute lymphoblastic leukemia. To investigate the mechanisms responsible for clofarabine resistance...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2014.11.001
更新日期：2015-03-01 00:00:00
abstract：OBJECTIVE:Although all-trans retinoic acid (ATRA) can bring about complete remission of acute promyelocytic leukemia (APL), the incidence of early recurrence is considerably high. Thus, chemotherapeutic agents, such as anthracycline agents or cytosine arabinoside (AraC), are generally co-administered with ATRA. The the...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00905-0
更新日期：2002-11-01 00:00:00
abstract：:The heat sensitivity at 42 degrees, 43 degrees and 44 degrees C of various hematopoietic subsets in murine bone marrow (MRA, CFU-S-12, CFU-S-8, CFU-GM, BFU-E and CFU-E) was investigated in order to determine whether there is a relationship between heat sensitivity and the position of cells within the stem cell hierarc...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-05-01 00:00:00
abstract：OBJECTIVE:We studied two adult brothers with severe congenital thrombocytopenia in order to determine the genetic etiology of their inherited disorder. Despite the absence of eczema or immunodeficiency, a mutation of the Wiskott-Aldrich syndrome (WAS) gene was suspected because of the presence of microthrombocytes. MA...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)01023-8
更新日期：2003-02-01 00:00:00
abstract：:In this study, we have used the sublethally irradiated rat as a model to examine the relationship between platelet count and the plasma level of megakaryocyte growth-promoting activity (Meg-GPA) assayed in vitro. Meg-GPA of irradiated rats whose platelet counts were maintained by platelet transfusions was compared to ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-02-01 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：: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
