Abstract：
OBJECTIVE:Mice harboring c-Myb hypomorphic mutations display enhanced thrombopoiesis because of increased numbers of megakaryocytes and their progenitors. Thrombopoietin induces these same effects, which lead us to hypothesize that the hormone acts through modulation of c-Myb expression, as c-Myb levels falls during thrombopoietin-induced megakaryocyte (MK) maturation. Micro RNAs (miRs) downregulate gene expression by binding to the 3' untranslated region (UTR) of specific messenger RNAs (mRNAs); we noted that the 3'UTR of c-Myb contains four miR-150 binding sites. MATERIALS AND METHODS:We used quantitative reverse transcriptase polymerase chain reaction, Western blotting, and reporter gene analyses to assess the response of c-Myb to thrombopoietin stimulation and to gain of and loss of miR-150 expression. RESULTS:We found that thrombopoietin reduced c-Myb mRNA and protein levels within 7 hours in megakaryocytes and UT7/thrombopoietin (TPO) cells. Using a reporter gene containing the c-Myb 3'UTR region, including its four miR150 binding sites, we found that expression of miR150 reduced luciferase expression to 50% of baseline at 24 hours and to 25% at 48 hours in UT7/TPO cells. Quantitative polymerase chain reaction and Western blotting also revealed that miR-150 reduced endogenous c-Myb mRNA and protein to 50% in UT7/TPO cells, and to 65% in mature megakaryocytes. Converse experiments utilizing anti-miR150 increased luciferase activity twofold over control anti-miR. Finally, TPO increased miR150 expression 1.8-fold within 24 hours and 3.4-fold within 48 hours. CONCLUSIONS:These findings establish that miR150 downmodulates c-Myb levels, and because TPO affects miR150 expression, our results indicate that, in addition to affecting MK progenitor cell growth, TPO downmodulates c-Myb expression through induction of miR-150.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Barroga CF,Pham H,Kaushansky Kdoi
10.1016/j.exphem.2008.07.001subject
Has Abstractpub_date
2008-12-01 00:00:00pages
1585-92issue
12eissn
0301-472Xissn
1873-2399pii
S0301-472X(08)00347-0journal_volume
36pub_type
杂志文章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：:Germinal center-associated nuclear protein (GANP) is a unique and multifunctional protein that plays a critical role in cell biology, neurodegenerative disorders, immunohematology, and oncogenesis. GANP is an orthologue of Saccharomyces Sac3, one of the components of the transcription export 2 (TREX-2) complex and a m...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2020.08.007
更新日期：2020-10-01 00:00:00
abstract：:12-O-tetradecanoylphorbol-13-acetate (TPA) has multiple effects on the capacity of human T-lymphocytes to form colonies in soft agar. This compound is directly mitogenic for T-lymphocytes; the optimal concentration (100 ng/ml) stimulates an average of 2862 +/- 583 colonies/7.5 X 10(5) cells plated. Furthermore, TPA ca...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1986-12-01 00:00:00
abstract：OBJECTIVE:Clonal stem cell proliferation and increased erythrocyte mass are hallmarks of the myeloproliferative disorder polycythemia vera (PV). The molecular basis of PV is unknown. METHODS:We carried out a genome-wide screening for loss of heterozygosity (LOH) and analyzed candidate genes within the LOH loci. RESUL...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(01)00789-5
更新日期：2002-03-01 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：:Activation of the N-ras gene via coding region mutations has been previously documented in 25% of patients with acute myeloid leukemia (AML). Since overexpression of normal N-ras is also transforming in vitro, the N-ras promoter of AML patients was analyzed for the presence of promoter mutations that may affect expres...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-09-01 00:00:00
abstract：OBJECTIVE:The CD15 (Lewis x) cell surface oligosaccharide moiety is expressed in a variety of normal and tumor cells and recognized by selectins. The detection of CD15 on malignant Hodgkin-Reed-Sternberg (HRS) cells serves as a diagnostic marker of Hodgkin's lymphoma (HL). Retrospective studies suggest that the express...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(03)00237-6
更新日期：2003-11-01 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：:The pool size of erythroid burst-(BFUe) and colony-forming units (CFUe) has been evaluated in normal or hypoxia-induced polycythemic mice at sequential times after either transfusion or administration of purified erythropoietin (Ep). The present investigations were focused on the in vitro tritiated thymidine (3H-TdR) ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-01-01 00:00:00
abstract：:Mice deprived of water for three days showed hemoconcentration due to a reduced plasma volume, suppressed erythropoiesis and reduced food intake. All three classes of erythroid progenitor cells in both the bone marrow and spleen of dehydrated mice were markedly suppressed but recovered rapidly upon rehydration. In add...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-05-01 00:00:00
abstract：:Decades-old findings supporting origin of F cells in adult life from adult-type progenitors and the in vitro and in vivo enhancement of fetal globin under stress conditions have been juxtaposed against recent mechanistic underpinnings. An updated molecular interrogation did not debunk prior conclusions on the origin o...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2020.09.195
更新日期：2020-12-01 00:00:00
abstract：OBJECTIVE:We examined the stimulatory effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production in male (NZW x BXSB) F(l) (W/B F(1)) mice, a murine model of idiopathic thrombocytopenic purpura. MATERIALS AND METHODS:A cohort of 19- to 25-week-old, severely t...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00898-6
更新日期：2002-10-01 00:00:00
abstract：:Interleukin (IL)-2 therapy given at tolerable doses is insufficient to induce maximum activation of natural killer (NK) cells. We recently demonstrated that NK cells expanded in vivo can be maximally activated by short-term ex vivo incubation with 1000 U/mL IL-2. However, IL-2 withdrawal, which would occur with reinfu...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1997-10-01 00:00:00
abstract：OBJECTIVE:The aim of this study was to evaluate the occurrence of T-cell spontaneous apoptosis (A(spont)) and its modulation in vitro by the interleukin-2 receptor (IL-2R) gamma-chain (gammac)-signaling cytokine IL-15 in patients transplanted with autologous peripheral blood progenitor cells (PBPC) for hematologic mali...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(01)00747-0
更新日期：2001-12-01 00:00:00
abstract：:Precise replacement of diseased or dysfunctional organs is the goal of regenerative medicine and has appeared to be a distant goal for a long time. In the field of hematopoietic stem cell transplantation, this goal is now becoming tangible as gene-editing technologies and novel conditioning agents are entering the cli...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2021.01.003
更新日期：2021-01-20 00:00:00
abstract：:Hepcidin is the key regulator of iron absorption and recycling, and its expression is suppressed by red blood cell production. When erythropoiesis is expanded, hepcidin expression decreases. To gain insight into the stage of erythroid differentiation at which the regulation might originate, we measured serum hepcidin ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2015.03.001
更新日期：2015-06-01 00:00:00
abstract：:The effect of staurosporine, a novel calcium/phospholipid-dependent protein kinase (protein kinase C) inhibitor, on differentiation of human promyelocytic leukemic HL-60 cells, was investigated. Staurosporine inhibited HL-60-cell proliferation in a concentration-dependent manner, but did not induce HL-60-cell differen...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-01-01 00:00:00
abstract：:Induced pluripotent stem cells (iPS) derived from disease cells are expected to provide a new experimental material, especially for diseases from which samples are difficult to obtain. In this study, we generated iPS from samples from patients with primary and secondary myelofibrosis. The primary myelofibrosis cells h...
journal_title：Experimental hematology
pub_type： 临床试验,杂志文章
doi：10.1016/j.exphem.2014.03.010
更新日期：2014-09-01 00:00:00
abstract：:The rae28 gene (rae28) is a murine homologue of the Drosophila polyhomeotic gene, which is a member of the Polycomb-group genes. In this study, we examined the role of rae28 in lymphocyte development. Because homozygous rae28-deficient (rae28-/-) mice died in the perinatal period, we examined lymphocyte development by...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(00)00620-2
更新日期：2001-01-01 00:00:00
abstract：:Previously, recombinant erythropoietin (rEpo) was shown to increase the number and size of megakaryocytic colonies in vitro, and in vivo it elevates the number of megakaryocytes in mouse spleens. To test the hypothesis that rEpo would stimulate platelet production in mice, both normal mice and mice in rebound-thromboc...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1987-07-01 00:00:00
abstract：OBJECTIVE:Many clinical gene therapy trials have described poor engraftment of retrovirally transduced CD34(+) cells. Because engraftment is dependent upon successful homing of graft cells to the bone marrow (BM), we examined whether retroviral-mediated gene transfer (RMGT) induces a homing defect in CD34(+) cells. ME...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2005.12.014
更新日期：2006-04-01 00:00:00
abstract：:Thrombocytopenia is an important clinical problem for many acquired immunodeficiency syndrome (AIDS) patients. Recently, the utility of recombinant cytokines in alleviating the hematopoietic complications of AIDS and AIDS therapy has been evaluated. The newly cloned cytokine stem cell factor (SCF) has been demonstrate...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-08-01 00:00:00
abstract：:A useful cytochemical technique has been developed which facilitates the identification of the types of cell aggregates which proliferate in soft agar cultures of hematopoietic stem cells. Staining of fixed agar discs for alpha-naphthyl acetate esterase (ANAE), naphthol AS-D chloroacetate esterase (CAE) and with Luxol...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1983-01-01 00:00:00
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：:Serum albumin has long been an essential supplement for ex vivo hematopoietic and immune cell cultures. However, serum albumin medium supplements represent a major source of biological contamination in cell cultures and often cause loss of cellular function. As serum albumin exhibits significant batch-to-batch variabi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2019.11.007
更新日期：2019-12-01 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：:The bcr/abl transcript is specifically expressed in the hematopoietic cells of patients with chronic myeloid leukemia (CML). The Haseloff and Gerlach model was used to design a ribozyme targeted to this transcript. When tested against a synthetic substrate covering the translocation sequence, the ribozyme exhibited si...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-12-01 00:00:00
abstract：OBJECTIVE:A complete process for mass generation of megakaryocytes from hematopoietic stem cells under serum-free conditions has great clinical potential for rapid platelet reconstruction in thrombocytopenia patients. We have previously reported on the generation of an optimized serum-free medium (serum-free hematopoie...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2009.07.012
更新日期：2009-11-01 00:00:00
abstract：:Rats with diets containing 0.2% propylthiouracil (PTU) throughout gestation had progeny with persistent cyanosis and high neonatal mortality. Histological and histochemical studies failed to reveal lung abnormalities in these pups. Studies of the blood of PTU-fed dams demonstrated that hemoglobin, packed cell volume, ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1982-01-01 00:00:00
abstract：:Megakaryocytic differentiation of progenitor cells was investigated in nine patients with low-risk myelodysplastic syndromes (MDS) (eight refractor anemia [RA] and one RA with ringed sideroblasts [RARS] and five patients with high-risk MDS (two RA with excess of blasts [RAEB] and three RAEB in transformation [RAEB-T])...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(98)00077-0
更新日期：1999-03-01 00:00:00
