Abstract:
:Thrombopoietin (Tpo), the ligand for c-mpl, has been shown to be the principal regulator of megakaryocytopoiesis and platelet production. The ability of Tpo to potently stimulate the growth of committed megakaryocyte (Mk) progenitor cells has been studied in detail. Murine fetal liver cells, highly enriched in primitive progenitors, have been shown to express c-mpl, but little is known about the ability of Tpo to stimulate the growth and differentiation of primitive multipotent bone marrow (BM) progenitor cells. Here, we show that Tpo alone and in combination with early acting cytokines can stimulate the growth and multilineage differentiation of Lin- Sca-1+ BM progenitor cells. In particular, Tpo potently synergized with the ligands for c-kit (stem cell factor [SCF]) and flt3 (FL) to stimulate an increase in the number and size of clones formed from Lin- Sca-1+ progenitors. When cells were plated at 1 cell per well, the synergistic effect of Tpo was observed both in fetal calf serum-supplemented and serum-depleted medium and was decreased if the addition of Tpo to cultures was delayed for as little as 24 hours, suggesting that Tpo is acting directly on the primitive progenitors. Tpo added to SCF + erythropoietin (Epo)-supplemented methylcellulose cultures potently enhanced the formation of multilineage colonies containing granulocytes, macrophages, erythrocytes, and Mks. SCF potently enhanced Tpo-stimulated production of high-ploidy Mks from Lin- Sca-1+ progenitors, whereas the increased growth response obtained when combining Tpo with FL did not translate into increased Mk production. The ability of Tpo and SCF to synergistically enhance the growth of Lin- Sca-1+ progenitors was predominantly observed in the more primitive rhodamine 123(lo) fraction. Tpo also enhanced growth of Lin- Sca-1+ progenitors when combined with interleukin-3 (IL-3) and IL-11 but not with IL-12, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, or Epo. Epo, which has high homology to Tpo, was unable to stimulate the growth of Lin- Sca-1+ progenitors alone or in combination with SCF or FL, suggesting that c-mpl is expressed on more primitive stages of progenitors than the Epo receptor. Thus, the present studies show the potent ability of Tpo to enhance the growth of primitive multipotent murine BM progenitors in combination with multiple early acting cytokines and documents its unique ability to synergize with SCF to enhance Mk production from such progenitors.
journal_name
Bloodjournal_title
Bloodauthors
Ramsfjell V,Borge OJ,Veiby OP,Cardier J,Murphy MJ Jr,Lyman SD,Lok S,Jacobsen SEsubject
Has Abstractpub_date
1996-12-15 00:00:00pages
4481-92issue
12eissn
0006-4971issn
1528-0020journal_volume
88pub_type
杂志文章相关文献
BLOOD文献大全abstract::Activation of p38 MAP kinase (p38) as well as JNK/SAPK has been described as being induced by a variety of environmental stresses such as osmotic shock, ultraviolet radiation, and heat shock, or the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1 (IL-1). We found that the hematopoietic cytokine...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-08-01 00:00:00
abstract::Adeno-associated virus (AAV)-based gene therapies can restore endogenous factor VIII (FVIII) expression in hemophilia A (HA). AAV vectors typically use a B-domain-deleted FVIII transgene, such as human FVIII-SQ in valoctocogene roxaparvovec (AAV5-FVIII-SQ). Surprisingly, the activity of transgene-produced FVIII-SQ was...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2020005683
更新日期:2020-11-26 00:00:00
abstract::One obstacle to retrovirus-mediated gene therapy for human hematopoietic disorders is the low efficiency of gene transfer into pluripotent hematopoietic stem cells (HSC). We have previously shown a direct correlation between retrovirus receptor mRNA levels in mouse HSC and the efficiency with which they are transduced...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-05-01 00:00:00
abstract::The transcription factor TAL1 has major functions during embryonic hematopoiesis and in adult erythropoiesis and megakaryocytopoiesis. These functions rely on different TAL1 structural domains that are responsible for dimerization, transactivation, and DNA binding. Previous work, most often done in mice, has shown tha...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-05-1689
更新日期:2004-05-01 00:00:00
abstract::The B-cell leukemia/lymphoma-2 (BCL-2) family of proteins governs the intrinsic pathway of mitochondrial apoptosis. Dysregulation of BCL-2 has long been known to be a crucial part of the pathophysiology of B-cell lymphomas; however, several early attempts to target this pathway therapeutically were unsuccessful becaus...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2017-04-737338
更新日期:2017-08-31 00:00:00
abstract::Erythroid (red blood) cells are the first cell type to be specified in the postimplantation mammalian embryo and serve highly specialized, essential functions throughout gestation and postnatal life. The existence of 2 developmentally and morphologically distinct erythroid lineages, primitive (embryonic) and definitiv...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2012-01-153486
更新日期:2012-05-24 00:00:00
abstract::Constitutively active JAK2V617F and thrombopoietin receptor (TpoR) W515L/K mutants are major determinants of human myeloproliferative neoplasms (MPNs). We show that a TpoRW515 mutation (W515A), which we detected in 2 myelofibrosis patients, and the Delta5TpoR active mutant, where the juxtamembrane R/KW(515)QFP motif i...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-10-183558
更新日期:2010-02-04 00:00:00
abstract::Hemophagocytic lymphohistiocytosis (HLH) is an often-fatal hyperinflammatory syndrome characterized by fever, hepatosplenomegaly, cytopenia, and in some cases hemophagocytosis. Here, we describe the mutation analysis, clinical presentation, and functional analysis of natural killer (NK) cells in patients with mutation...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-05-282541
更新日期:2010-10-14 00:00:00
abstract::The receptor for hyaluronic acid-mediated motility (RHAMM/CD168) has been described as a leukemia-associated antigen. To define T-cell epitopes of RHAMM/CD168 toward specific immunotherapies for acute myeloid leukemia (AML), 10 potential HLA-A2-binding RHAMM/CD168 peptides (R1 to R10) were synthesized based on compute...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-12-4787
更新日期:2005-08-01 00:00:00
abstract::"Fetal" erythrocytes are present in older children and certain adults with hematologic disorders. To determine if regenerating bone marrow produces such cells, we examined the blood of seven allogeneic bone marrow transplant recipients. Six patients were engrafted with donor cells, while on e patients recovered autolo...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1976-12-01 00:00:00
abstract::Deficiency of functional deoxycytidine kinase (dCK) is a common characteristic for in vitro resistance to cytarabine (AraC). To investigate whether dCK is also a target for induction of AraC resistance in patients with acute myeloid leukemia (AML), we determined dCK messenger RNA (mRNA) expression in (purified) leukem...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-08-15 00:00:00
abstract::We have conducted a pilot study to investigate the role of high-dose therapy and autologous bone marrow/stem cell transplantation (ASCT) during first complete or partial remission in 52 patients with poor-risk aggressive lymphoma. There were 42 patients with intermediate-grade or immunoblastic lymphoma who were consid...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:
更新日期:1997-11-15 00:00:00
abstract::Hypersensitivity to cross-linking agents and predisposition to malignancy are characteristic of the genetically heterogeneous inherited bone marrow failure syndrome, Fanconi anemia (FA). The protein encoded by the recently cloned FA complementation group A gene, FAA, has been expected to localize in the nucleus as bas...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-11-01 00:00:00
abstract::Acquired factor XIII (FXIII) deficiency due to autoantibody against FXIII is a very rare severe hemorrhagic diathesis. Antibodies directed against the A subunit of FXIII, which interfere with different functions of FXIII, have been described. Here, for the first time, we report an autoantibody against the B subunit of...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-09-179333
更新日期:2009-01-15 00:00:00
abstract::Gadd45a has been involved in DNA damage response and in many malignancies, including leukemia. However, the function of Gadd45a in hematopoietic stem cells (HSCs) remains unknown. Here, we reported that Gadd45a-deficient (Gadd45a(-/-)) mice showed a normal hematologic phenotype under homeostatic conditions. However, f...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-05-504084
更新日期:2014-02-06 00:00:00
abstract::The proapoptotic function of p53 is thought to underlie most anticancer modalities and is also activated in response to oncogenic insults, such as overexpression of the Myc oncoprotein. Here we generated tractable B lymphomas using retroviral transduction of the MYC oncogene into hematopoietic cells with 2 knock-in al...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-10-050294
更新日期:2007-06-01 00:00:00
abstract::Single-center experiences have shown that intensified treatments with autologous transplantation are a promising therapeutic strategy for patients with high-risk follicle-center lymphoma (FCL) at diagnosis, whereas data from prospective multicenter trials are still lacking. This paper describes the results of a prospe...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1182/blood-2002-02-0621
更新日期:2002-09-01 00:00:00
abstract::Platelet factor 4 (PF4) is an abundant platelet alpha-granule C-X-C chemokine that has weak chemotactic potency but strongly inhibits hematopoiesis through an unknown mechanism. We find that PF4 binds to human CD34+ hematopoietic progenitor cells (HPCs) with a median effective concentration of 1 microg/mL but not afte...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-08-2363
更新日期:2003-06-15 00:00:00
abstract::Osteolytic bone destruction and its complications, bone pain, pathologic fractures, and hypercalcemia, are a major source of morbidity and mortality in patients with multiple myeloma. The bone destruction in multiple myeloma is due to increased osteoclast (OCL) activity and decreased bone formation in areas of bone ad...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-02-15 00:00:00
abstract::Exposure to ambient particulate matter (PM) air pollution has been reported to trigger inflammation and thrombosis. However, molecular mechanisms underlying the modulation of coagulation pathways in PM-induced thrombosis remain largely unknown. We report here that Sirt1, a member of class III histone deacetylase, cont...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-04-350413
更新日期:2012-03-08 00:00:00
abstract::Transforming mutations in NRAS and KRAS are thought to play a causative role in the development of numerous cancers, including myeloid malignancies. Although mutations at amino acids 12, 13, or 61 account for the majority of oncogenic Ras variants, we hypothesized that less frequent mutations at alternate residues may...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-04-152157
更新日期:2009-02-19 00:00:00
abstract::The retinoblastoma (Rb) tumor suppressor plays important roles in regulating hematopoiesis, particularly erythropoiesis. In an effort to understand whether Rb function can be mediated by E2F transcription factors in a BM-derived hematopoietic system in mice, we uncovered a functional synergy between Rb and E2F8 to pro...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-10-388231
更新日期:2012-05-10 00:00:00
abstract::In order to determine the prognostic significance of thrombocytosis in idiopathic sideroblastic anemia, the clinical courses of 17 patients were reviewed. Six patients (36%) had thrombocytosis, and none developed acute leukemia. Nine patients (53%) had normal platelet counts, and one developed acute leukemia. Two pati...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1977-09-01 00:00:00
abstract::The transcription repressor BCL-6 is known to play critical roles in B-cell lymphomagenesis, germinal center formation, and balanced Th1/Th2 differentiation. In macrophages, although BCL-6 has also been shown to regulate the expression of several chemokine genes, its function in other aspects of macrophage biology has...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-08-3171
更新日期:2005-02-15 00:00:00
abstract::Using a polyclonal antiserum against canine CD34, we previously found that CD34 is expressed on canine bone marrow progenitor cells in a manner analogous to that found in humans. To further characterize CD34+ cells and to facilitate preclinical canine stem cell transplant studies, monoclonal antibodies (MoAbs) were ra...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-03-15 00:00:00
abstract::Anticoagulation with vitamin K antagonists (VKAs) is problematic because of difficulties in safely managing dosing. Polymorphisms in cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase genes (VKORC1) have been shown to affect VKA dosing in adults. The association of these polymorphisms on VKA dosing in childr...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-05-283861
更新日期:2010-12-23 00:00:00
abstract::Increased expression levels of miR-181 family members have been shown to be associated with favorable outcome in patients with cytogenetically normal acute myeloid leukemia. Here we show that increased expression of miR-181a and miR-181b is also significantly (P < .05; Cox regression) associated with favorable overall...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-10-386235
更新日期:2012-03-08 00:00:00
abstract::Most studies of mammalian reticulocyte maturation have used blood reticulocytes. Nascent reticulocytes, as found in bone marrow, have not been available in developmentally synchronized populations. Nascent murine reticulocytes formed in vitro by enucleation of Friend virus-infected erythroblasts were purified and recu...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-02-0616
更新日期:2005-03-01 00:00:00
abstract::Washed human platelets were labeled with 125I by the lactoperoxidase-catalyzed method and solubilized in 1% Triton X-100. The soluble proteins were analyzed by crossed-immunoelectrophoresis in 1% agarose, employing a rabbit antibody raised against whole human platelets. Analysis of autoradiograms developed from dried ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1981-12-01 00:00:00
abstract::The incidence of neutralizing isoantibody formation to infused factor VIII in a cohort of 67 hemophilia A patients, born between January 1, 1971 and April 30, 1990, who had been treated exclusively with lyophilized cryoprecipitate, was 6% (5.3 per 1,000 patient years of observation). The age-dependent cumulative risk ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-06-15 00:00:00