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 withstand myeloablative chemotherapy or effectively transplant irradiated recipient mice. A similar phenotype has been observed for Prdm16, except that the Prdm16 constitutive knockout is lethal. Here, we created a novel double-knockout model of Mds1-Evi1 and Prdm16 in the bone marrow, in which double knockout occurs only in cells that endogenously express Mds1-Evi1 and only upon induction with tamoxifen. We show that combined Mds1-Evi1/Prdm16 deficiency causes bone marrow failure within 15 days, with rapid loss in all progenitor compartments, while the peripheral blood exhibits progressive reductions in peripheral monocytes and granulocytes. We found that surviving hematopoietic stem cells and granulocytic progenitors had elevated apoptosis and cell division, and were unable to form colonies in vitro; adding back wild-type Mds1-Evi1 or Prdm16 to double-knockout bone marrow restores colony formation, and for MDS1-EVI1, this activity depends on a functional PR domain. All of these phenotypic effects were exhibited at milder levels in Mds1-Evi1 and Prdm16 single-knockout controls. Overall, these results illustrate that Mds1-Evi1 and Prdm16 play additive roles in maintaining normal hematopoietic stem cell survival.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
McGlynn KA,Sun R,Vonica A,Rudzinskas S,Zhang Y,Perkins ASdoi
10.1016/j.exphem.2020.04.010subject
Has Abstractpub_date
2020-05-01 00:00:00pages
20-32.e3eissn
0301-472Xissn
1873-2399pii
S0301-472X(20)30148-Xjournal_volume
85pub_type
杂志文章abstract：:Transforming growth factor β (TGFβ) is a potent inhibitor of hematopoietic stem and progenitor cell proliferation. However, the precise mechanism for this effect is unknown. Here, we have identified the transcription factor Gata2, previously described as an important regulator of hematopoietic stem cell function, as a...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2016.02.001
更新日期：2016-05-01 00:00:00
abstract：:More than 2million human erythroblasts extrude their nuclei every second in bone marrow under hypoxic conditions (<7% O2). Enucleation requires specific signal transduction pathways and the local assembly of contractile actomyosin rings. However, the energy source driving these events has not yet been identified. We e...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2019.02.004
更新日期：2019-04-01 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: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：: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...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2017.05.004
更新日期：2017-08-01 00:00:00
abstract：OBJECTIVE:Among Philadelphia chromosome-negative myeloproliferative neoplasms (Ph(-) MPN), essential thrombocythemia (ET) and the prefibrotic phase of primary myelofibrosis (PMF) represent two subtypes with considerable overlap. MATERIALS AND METHODS:In this study, histopathological classification of 490 MPN cases was...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2009.07.005
更新日期：2009-10-01 00:00:00
abstract：OBJECTIVE:Polycythemia vera (PV) is characterized by erythrocytosis associated with the presence of the activating JAK2(V617F) mutation in a variable proportion of hematopoietic cells. JAK2(V617F) is detected in other myeloproliferative neoplasms, does not appear to be the PV-initiating event, and its specific role in ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2009.09.009
更新日期：2009-12-01 00:00:00
abstract：OBJECTIVE:Monoclonal antibody (mAb) 9C4 detects a surface antigen expressed on immature erythroid progenitor cells and epithelial tumor cell lines. The aim of this study was to identify the recognized surface antigen and to analyze a potential role of this molecule in early steps of erythropoiesis. MATERIALS AND METHO...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00798-1
更新日期：2002-06-01 00:00:00
abstract：OBJECTIVE:We previously reported on the heterogeneity of bone marrow stromal cell function in supporting hematopoietic cell proliferation and differentiation in vitro among refractory anemia (RA) of myelodysplastic syndrome (MDS) patients. Interestingly, stromal cells from some MDS RA patients induced an apoptotic chan...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(99)00142-3
更新日期：2000-02-01 00:00:00
abstract：:Several prospective randomized trials in acute myelocytic leukemia (AML) documented a lower relapse rate with autologous bone marrow transplantation (ABMT) than with conventional chemotherapy. However, they also identified some transplant difficulties, such as failure to collect sufficient numbers of stem cells, slow ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(99)00121-6
更新日期：1999-12-01 00:00:00
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 hem...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.04.001
更新日期：2006-08-01 00:00:00
abstract：:Chronic myeloid leukemia (CML) is caused by Bcr-Abl, a constitutively active tyrosine kinase that is the result of a reciprocal translocation between chromosomes 9 and 22 and cytogenetically evident as the Philadelphia chromosome. Imatinib (Glivec, Gleevec), a specific small molecule inhibitor of Bcr-Abl, has become t...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2007.01.023
更新日期：2007-04-01 00:00:00
abstract：OBJECTIVE:Activating mutations in FLT3 are known to be a frequent transforming event in acute myeloid leukemia. Small molecule-inhibitor therapy targeting the FLT3 kinase is, therefore, an attractive strategy. FLT3 kinase inhibitors, such as PKC412, have already entered clinical trials. Even though results are encourag...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.07.008
更新日期：2007-10-01 00:00:00
abstract：OBJECTIVE:The ABCG2 transporter has been identified as a determinant of the side population (SP) in murine bone marrow and a potential marker for primitive stem cells. To assess the potential of the SP phenotype and ABCG2 expression to identify stem cells in human umbilical cord blood (hUCB), we have examined directly ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.09.015
更新日期：2009-02-01 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：: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：BACKGROUND:Autologous bone marrow transplantation is an important therapy for patients with acute myelogenous leukemia (AML). However, leukemia in the graft may contribute to posttransplant relapse. Treatment of the graft with 4-hydroperoxycyclophosphamide (4HC) is sometimes used to decrease numbers of infused leukemia...
journal_title：Experimental hematology
pub_type： 杂志文章,多中心研究
doi：10.1016/s0301-472x(01)00732-9
更新日期：2001-11-01 00:00:00
abstract：OBJECTIVE:These studies were performed to test the hypothesis that DNMT1 is required for maintenance of DNA methylation and repression of the γ-globin gene in adult-stage erythroid cells. MATERIALS AND METHODS:DNMT1 levels were reduced by nucleofection of small interfering RNA targeting DNMT1 in chemical inducer of di...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2010.10.003
更新日期：2011-01-01 00:00:00
abstract：:Studies were undertaken to produce monoclonal antibodies directed against the murine receptor for macrophage colony-stimulating factor (M-CSF or CSF-1). Sprague-Dawley rats were injected with lysates prepared from a murine myelomonocytic cell line (RAW cell line) that has high levels of M-CSF receptors. Spleen cells f...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-04-01 00:00:00
abstract：:T(4;11) MLL-AF4 acute leukemia is one of the most aggressive malignancies in infant and pediatric populations. Epidemiological and functional studies have highlighted the influence of an overstimulation of the immune system on leukemia development. This study aimed at assessing if the cell-of-origin of t(4;11) MLL-AF4...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2019.07.004
更新日期：2019-08-01 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：: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 results and complications of 224 marrow collections from 200 patients with malignant disease who underwent marrow aspiration and storage for subsequent autologous marrow transplantation (AMT) were analyzed. The median age of the patients was 35 years (range 1-68); 131 patients had hematologic malignancies and 69 h...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1985-10-01 00:00:00
abstract：:Fractionated whole body irradiation induces thymic lymphomas in C57 BL/Ka mice after 6-12 months. A graft of normal congenic bone marrow cells immediately after the last irradiation prevents the development of lymphomas by inducing the disappearance of preleukemic cells. When such a graft is performed one month later,...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1997-02-01 00:00:00
abstract：:A method is described that permits the removal of hematopoietic cells and macrophages from mouse bone marrow cultures. The method is based on the difference in effect of extracellular ATP4- ions (ATP in the absence of divalent, complexing cations) on cells of hematopoietic origin, including macrophages, and of nonhema...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1994-02-01 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：:Mouse bone marrow cells were cultured to determine some basic characteristics of the diffusion chamber (DC) technique. The main findings were as follows: (i) Incorporated 3H-thymidine was conveniently measured after deposition of a cell sample on glass fibre discs followed by methanol washing. Varying the specific act...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1975-08-01 00:00:00
abstract：:Exosomes are virus-size membrane-bound vesicles of endocytic origin present in all body fluids. Plasma of AML patients is significantly enriched in exosomes, which carry a cargo of immunosuppressive molecules and deliver them to recipient immune cells, suppressing their functions. However, whether these exosomes origi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2019.07.005
更新日期：2019-08-01 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：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
