Abstract:
:Sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1) is a (deoxy)guanosine triphosphate (dGTP/GTP)-activated deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase involved in cellular dNTP homoeostasis. Mutations in SAMHD1 have been associated with the hyperinflammatory disease Aicardi-Goutières syndrome (AGS). SAMHD1 also limits cells' permissiveness to infection with diverse viruses, including human immunodeficiency virus (HIV-1), and controls endogenous retroviruses. Increasing evidence supports the role of SAMHD1 as a tumor suppressor. However, SAMHD1 also can act as a resistance factor to nucleoside-based chemotherapies by hydrolyzing their active triphosphate metabolites, thereby reducing response of various malignancies to these anticancer drugs. Hence, informed cancer therapies must take into account the ambiguous properties of SAMHD1 as both an inhibitor of uncontrolled proliferation and a resistance factor limiting the efficacy of anticancer treatments. Here, we provide evidence that SAMHD1 is a double-edged sword for patients with acute myelogenous leukemia (AML). Our time-dependent analyses of The Cancer Genome Atlas (TCGA) AML cohort indicate that high expression of SAMHD1, even though it critically limits the efficacy of high-dose ara-C therapy, might be associated with more favorable disease progression.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Herold N,Rudd SG,Sanjiv K,Kutzner J,Myrberg IH,Paulin CBJ,Olsen TK,Helleday T,Henter JI,Schaller Tdoi
10.1016/j.exphem.2017.05.001subject
Has Abstractpub_date
2017-08-01 00:00:00pages
32-39eissn
0301-472Xissn
1873-2399pii
S0301-472X(17)30144-3journal_volume
52pub_type
杂志文章abstract:OBJECTIVE:We studied immune reconstitution in 51 recipients of HLA-identical hematopoietic cellular transplant (HCT) after nonmyeloablative conditioning compared to a reference group of 67 recipients after myeloablative conditioning. METHODS:Nonmyeloablative conditioning consisted of 2 Gy total-body irradiation+/-flud...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(03)00201-7
更新日期:2003-10-01 00:00:00
abstract::Two types of murine marrow adherent cells derived from Dexter cultures have been characterized. Exposure of C57B1/6J, ICR, or BDF1 mice to 1000 R x-ray 24 h prior to killing and establishment of liquid marrow cultures resulted in the growth of two types of adherent cells. A macrophage-like cell was phagocytic, nonspec...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1984-08-01 00:00:00
abstract::Marrow from Sl/Sld mice (in which the hemopoietic stromal microenvironment is defective), when implanted beneath the renal capsule of a normal littermate, produces an ectopic marrow site containing the same number of stem cells (CFU-S) and nearly as many GM-CFC as that obtained by implanting marrow from a normal litte...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-03-01 00:00:00
abstract::An increasing amount of data provides strong evidence for the complex multifactorial control of primary hemopoietic functions. Here we present a new multicellular functional unit, the Hematon, isolated from the light-density floating fraction of normal human bone marrow (BM) aspirates. The Hematon is organized in a co...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-05-01 00:00:00
abstract::[3H]thymidine uptake by NFS-60 cells in microcultures was found to increase in a linear fashion with the increasing doses of purified recombinant human granulocyte colony-stimulating factor (rhG-CSF). Such increases were found neither with rhG-CSF samples pretreated with rabbit anti-rhG-CSF serum nor with other human ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-02-01 00:00:00
abstract::To characterize hematopoietic cell biology, many investigators have used protocols that enrich for primitive hematopoietic stem cells (PHSC). In this study, we quantified the long-term repopulating ability (LTRA) of enriched and discarded fractions of PHSC from day-14 murine fetal liver using the competitive repopulat...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::The production of interferon-alpha (IFN-alpha) by normal human peripheral blood mononuclear cells (PBMNC) was studied using polyclonal antipeptide antibodies designed to react either with all IFN-alpha subtypes or with individual subtypes IFN-alpha 2 or IFN-alpha 4. In this study, we demonstrate the detection of intra...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract::Pathogenesis of cytomegalovirus (CMV)-induced myelosuppression is not clearly understood and could be related to a direct toxic effect on the marrow progenitors and/or an alteration of the marrow environment. Myeloid progenitors (granulocyte-macrophage colony-forming units, CFU-GM) were not affected by incubation with...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-02-01 00:00:00
abstract::Distinctive patterns of chromatin modification control gene expression and define cellular identity during development and cell differentiation. Polycomb repressive complex 2 (PRC2), the sole mammalian enzymatic complex capable of establishing gene-repressive high-degree methylation of histone H3 at lysine 27 (H3K27),...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2015.05.001
更新日期:2015-08-01 00:00:00
abstract::Chloramphenicol, an antibiotic associated with reversible bone marrow suppression and fatal aplastic anemia, was found to increase human bone marrow granulocyte-macrophage colonies (CFU-GM) in vitro. Maximal stimulation was at a concentration of 1.0 micrograms/ml (3.1 microM), with inhibition at concentrations greater...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-02-01 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::We have attempted to evaluate in vivo effects of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on acute radiation hematopoietic injury in mice. BDF1 mice, irradiated with 7.5-Gy x-rays, were injected i.p. twice daily for 10 days with 10(5) U recombinant hum...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-09-01 00:00:00
abstract:OBJECTIVE:Potent immunosuppressants, such as rapamycin, FK506, and ascomycin, are known to regulate the phosphorylation of proteins. The purpose of this study was to investigate the effects of these immunosuppressants on differentiation of several human myeloid leukemic cell lines. MATERIALS AND METHODS:Human myeloid ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00626-9
更新日期:2001-05-01 00:00:00
abstract::Bone marrow hematopoietic progenitors (CFU-GM, CFU-E, and BFU-E) were found to be markedly decreased in 21 bone marrow transplant recipients studied from one to 51 months after transplantation. In these patients, bone marrow colony formation could be significantly enhanced by in vitro incubation of the bone marrow tar...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-08-01 00:00:00
abstract::In the accompanying paper we constructed a model for the proliferation and differentiation of granulocyte-macrophage progenitor cells in response to the specific proliferation/differentiation stimulus granulocyte-macrophage colony-stimulating activity (gm-CSA). Here we have tested the model without altering the model ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-02-01 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::Serum obtained from (C3H X C57BL) F1 hybrid mice injected with parental (C57BL) lymph node cells after 600 rad irradiation contained a high level of an erythropoietic factor, which enhanced erythroid colony formation by fetal C57BL liver cells in methylcellulose cultures. The serum level of this erythroid colony-stimu...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1984-11-01 00:00:00
abstract::Addition of carbamylcholine, a cholinergic analogue, to bone marrow cultures enhanced megakaryocytic and granulocytic growth by 60% and 42%, respectively. When carbamylcholine was added to spleen cells cultured in the presence of pokeweed mitogen, the resulting conditioned medium (PWM-SCM) increased the number of mega...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-12-01 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::Haploinsufficiency of erythroid Krüppel-like factor (EKLF/KLF1) has been shown recently to ameliorate the clinical severity of β-thalassemia by increased expression levels of fetal hemoglobin (HbF). The underlying mechanisms for role of EKLF in regulating HbF are of great interest but remain incompletely understood. I...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2018.03.004
更新日期:2018-07-01 00:00:00
abstract::The high affinity Fc gamma receptor, Fc gamma RI, is unique among the three classes of macrophage Fc gamma receptors not only in its affinity for IgG, but also in the structure of its cytoplasmic domain. Fc gamma RIIA and the gamma subunit of Fc gamma RIIIA have tyrosine-containing motifs within their cytoplasmic doma...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1994-07-01 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::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::Unlike cell lines, human hematopoietic stem cells (HSCs) are less efficiently transduced with HIV-1 vectors, potentially limiting this approach. To investigate which step (internalization, reverse transcription, nuclear transport, and integration) limits lentiviral transduction, we evaluated the kinetics of lentiviral...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2015.10.003
更新日期:2016-02-01 00:00:00
abstract:OBJECTIVE:Recognition of E- and P-selectins on vascular endothelium by their leukocyte glycoprotein counterreceptor P-selectin glycoprotein ligand-1 (PSGL-1) initiates and sustains leukocyte rolling, culminating in extravasation of lymphocytes from blood into organs. PSGL-1 is rendered functional by terminal glycosylat...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.08.003
更新日期:2005-12-01 00:00:00
abstract::Cell-lineage involvement in a typical case of chronic myelomonocytic leukemia (CMML) was examined by simultaneous analysis of morphology and chromosomes on the same single colonies. Cytogenetic analysis of patient's bone marrow cells showed two clones: 46,X,-Y,+M1 (63/68 cells) and 47,X,-Y,+M1,+M2 (5/68 cells). Bone m...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-05-01 00:00:00
abstract::We analyzed the accessory function of malignant B cells from non-Hodgkin's lymphomas (NHLs). Among the 70 samples of malignant B cells included, four patterns of expression of the costimulatory molecules CD80 and CD86 were distinguished (+/+, +/-, -/+ and -/-). In two-thirds of the cases, CD80, CD86, or both were expr...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(98)00059-9
更新日期:1999-03-01 00:00:00
abstract:OBJECTIVE:To investigate whether Flk1(+)CD31(-)CD34(-) cells isolated from fetal bone marrow (BM) have characteristics of hemangioblasts, i.e., progenitors of endothelial and hematopoietic cells. MATERIALS AND METHODS:Mononuclear cells from fetal BM were negatively sorted by CD45, GlyA, and CD34 micromagnetic beads, t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(03)00087-0
更新日期:2003-07-01 00:00:00
abstract::In vitro colony formation by erythroid progenitors from the bone marrow was studied in 42 patients with a myelodysplastic syndrome using both a standard assay for growing erythroid colonies and an assay designed for growing megakaryocyte colonies. In the standard assay 5 patients had normal numbers of erythroid burst-...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-11-01 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