Acute toxic effects of 3'-azido-3'-deoxythymidine (AZT) on normal and regenerating murine hematopoiesis.

Abstract:

:The immediate hematopoietic response to 3'-azido-3'-deoxythymidine (AZT) was characterized in an unperturbed and regenerating mouse marrow model to identify the in vivo hematopoietic targets of AZT and test whether AZT toxicity is dependent on the proliferative activity of the hematopoietic targets. B6D2F1 mice received intravenous (IV) bolus injections of 30, 60, 120, and 240 mg/kg AZT. None of the doses induced consistent changes in the number of hematopoietic stem and progenitor cells. However, identical cumulative doses administered as an intravenous 24-hour infusion led to marked changes. Spleen colony-forming units (CFU-S) per femur were diminished to about 60%. Burst-forming units-erythroid (BFU-E) and colony-forming units-erythroid (CFU-E) were substantially reduced to about 15 to 35% at the two highest doses, whereas the femoral content of colony-forming units-granulocyte/macrophage (CFU-GM) and colony-forming units-megakaryocyte (CFU-Meg) was unchanged. When administered to mice whose marrow was regenerating from total-body irradiation (TBI) and subsequent bone marrow transplantation (high proliferative fraction), 240 mg/kg AZT caused considerable reductions of all hematopoietic cell stages even when given as a single IV injection. The results indicate that (1) the mode of application is critical for AZT hematotoxicity; (2) erythropoietic progenitors are the most sensitive to AZT toxicity; and (3) hematotoxicity increases with increasing proliferative activity.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

Scheding S,Media JE,Nakeff A

subject

Has Abstract

pub_date

1994-01-01 00:00:00

pages

60-5

issue

1

eissn

0301-472X

issn

1873-2399

journal_volume

22

pub_type

杂志文章
  • Assessment of the role of timing of second transplantation in multiple myeloma by multistate modeling.

    abstract:OBJECTIVE:Stem cell transplantation has a place in the management of many patients with hematological disorders, but is no longer the final and definitive treatment for most of these individuals. The relapsing patient may be offered further therapy, and evaluating the contribution of the treatments available has become...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/j.exphem.2008.06.007

    authors: Iacobelli S,Apperley J,Morris C

    更新日期:2008-11-01 00:00:00

  • A selective culture system for generating terminal deoxynucleotidyl transferase-positive lymphoid precursor cells in vitro. IV. Properties and developmental relationships of the lymphoid cells in the adherent and nonadherent compartments of the culture.

    abstract::In a selective culture system, the in vitro generation of terminal deoxynucleotidyl transferase positive (TdT+) B cell progenitors from rat, mouse, and human bone marrow (BM) is characterized by initial lymphoid colonization of a mouse BM feeder layer. In the present study, four sequentially appearing subsets of B cel...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: McKenna SD,Medlock ES,Greiner DL,Goldschneider I

    更新日期:1994-11-01 00:00:00

  • NK cell colony formation from human fetal thymocytes.

    abstract::We established a clonal cell culture system for human natural killer (NK) cells from fetal thymocytes. Thymocytes of 16 to 22 gestational weeks were cultured in methylcellulose in the presence of interleukin (IL)-7, IL-15, and steel factor (SF). After 14 days in incubation, large, diffuse colonies consisting of small ...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/s0301-472x(99)00005-3

    authors: Sato T,Laver JH,Aiba Y,Ogawa M

    更新日期:1999-04-01 00:00:00

  • A regulatory circuitry between miR-193a/miR-600 and WT1 enhances leukemogenesis in acute myeloid leukemia.

    abstract::The aberrant overexpression of Wilms tumor-1 (WT1) in acute myeloid leukemia (AML) plays an important role in blast cell survival by enhancing proliferation and inhibiting apoptosis. However, the mechanism underlying the overexpression of WT1 remains unclear. Here, we identified miR-193a (miR-193a-5p) and miR-600 targ...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/j.exphem.2018.02.001

    authors: Li H,Xing C,Zhou B,Ye H,Feng J,Wu J,Gao S

    更新日期:2018-05-01 00:00:00

  • Oncogenic Ras blocks transforming growth factor-beta-induced cell-cycle arrest by degradation of p27 through a MEK/Erk/SKP2-dependent pathway.

    abstract:OBJECTIVE:To examine whether oncogenic Ras affects transforming growth factor (TGF)-beta-mediated cell-cycle arrest in hematopoietic cells and the downstream signal transduction pathway involved in the interference with TGF-beta-induced cell-cycle arrest. MATERIALS AND METHODS:Two leukemic cell lines bearing N-Ras(L61...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/j.exphem.2005.04.006

    authors: Schepers H,Wierenga AT,Eggen BJ,Vellenga E

    更新日期:2005-07-01 00:00:00

  • Genome-wide DNA-mapping of CD34+ cells from patients with myelodysplastic syndrome using 500K SNP arrays identifies significant regions of deletion and uniparental disomy.

    abstract:OBJECTIVE:Identification of genomic lesions in progenitor cells of patients with myelodysplastic syndrome (MDS) could lead to the discovery of new disease-specific genes and may be of prognostic value. MATERIALS AND METHODS:We carried out a genome-wide mapping of DNA from CD34+ cells of MDS patients with high-resoluti...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/j.exphem.2008.10.012

    authors: Nowak D,Nolte F,Mossner M,Nowak V,Baldus CD,Hopfer O,Noll S,Thiel E,Wagner F,Hofmann WK

    更新日期:2009-02-01 00:00:00

  • A randomized multicenter comparison of CD34(+)-selected progenitor cells from blood vs from bone marrow in recipients of HLA-identical allogeneic transplants for hematological malignancies.

    abstract:OBJECTIVE:Peripheral blood progenitor cells (PBPC) have been established as an alternative source of hematopoietic stem cells for allogeneic transplantation, but an increased incidence of both acute and chronic graft-vs-host disease (GVHD) has become apparent. We performed a prospective randomized trial comparing bone ...

    journal_title:Experimental hematology

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1016/s0301-472x(03)00195-4

    authors: Cornelissen JJ,van der Holt B,Petersen EJ,Vindelov L,Russel CA,Höglund M,Maertens J,Schouten HC,Braakman E,Steijaert MM,Zijlmans MJ,Slaper-Cortenbach I,Boogaerts MA,Löwenberg B,Verdonck LF

    更新日期:2003-10-01 00:00:00

  • Hematopoietic origins of fibroblasts: II. In vitro studies of fibroblasts, CFU-F, and fibrocytes.

    abstract:OBJECTIVE:Using transplantation of a clonal population of cells derived from a single hematopoietic stem cell (HSC) of transgenic enhanced green fluorescent protein (EGFP) mice, we have documented the hematopoietic origin of myofibroblasts, such as kidney mesangial cells and brain microglial cells. Because myofibroblas...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/j.exphem.2005.10.008

    authors: Ebihara Y,Masuya M,Larue AC,Fleming PA,Visconti RP,Minamiguchi H,Drake CJ,Ogawa M

    更新日期:2006-02-01 00:00:00

  • Multiparameter analysis of transplantable hemopoietic stem cells. II. Stem cells of long-term bone marrow-reconstituted recipients.

    abstract::Marrow obtained from mice (referred to as [X + BM] mice) 3 months after gamma-irradiation (9 Gy) and bone marrow inoculation (0.1 femur equivalents) showed a reduced capacity to reconstitute hemopoiesis of irradiated mice and an increased sensitivity to 5-fluorouracil. Sorting of marrow from (X + BM) mice on the basis...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: Bertoncello I,Hodgson GS,Bradley TR

    更新日期:1988-05-01 00:00:00

  • Agonists to the A3 adenosine receptor induce G-CSF production via NF-kappaB activation: a new class of myeloprotective agents.

    abstract:OBJECTIVE:The aim of this study was to evaluate the effect of CF101, a synthetic agonist to the A3 adenosine receptor (A3AR), on the production of granulocyte colony-stimulating factor (G-CSF). The ability of CF101 to act as a myeloprotective agent in chemotherapy-treated mice was tested. METHODS:CF101 was administere...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/s0301-472x(02)00962-1

    authors: Bar-Yehuda S,Madi L,Barak D,Mittelman M,Ardon E,Ochaion A,Cohn S,Fishman P

    更新日期:2002-12-01 00:00:00

  • Molecularly cloned and expressed murine T-cell gene product is biologically similar to interleukin-3.

    abstract::Clonal lines of mouse inducer ly1+ly2- inducer T-lymphocytes that depend for growth upon interleukin-2 have been demonstrated to produce a factor that stimulates colony formation by bone marrow granulocyte-macrophage (GM-CFUc) progenitor cells and replication of factor-dependent mast cell/basophil and multipotential h...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: Greenberger JS,Humphries RK,Messner H,Reid DM,Sakakeeny MA

    更新日期:1985-05-01 00:00:00

  • Targeted gene correction of RUNX1 in induced pluripotent stem cells derived from familial platelet disorder with propensity to myeloid malignancy restores normal megakaryopoiesis.

    abstract::Familial platelet disorder with propensity to acute myeloid leukemia (FPD/AML) is an autosomal dominant disease associated with a germline mutation in the RUNX1 gene and is characterized by thrombocytopenia and an increased risk of developing myeloid malignancies. We generated induced pluripotent stem cells (iPSCs) fr...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/j.exphem.2015.05.004

    authors: Iizuka H,Kagoya Y,Kataoka K,Yoshimi A,Miyauchi M,Taoka K,Kumano K,Yamamoto T,Hotta A,Arai S,Kurokawa M

    更新日期:2015-10-01 00:00:00

  • Effects of escalating doses of recombinant human interleukin-2 in correcting functional T-cell defects following autologous bone marrow transplantation for lymphomas and solid tumors.

    abstract::High-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) in the treatment of malignancies is often associated with immune deficiency following transplantation, possibly contributing to tumor relapse or fatal infection. Interleukin 2 (IL-2), which enhances major histocompatibility complex (MHC)-...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: Bosly A,Guillaume T,Brice P,Humblet Y,Staquet P,Doyen C,Chatelain B,Franks CR,Gisselbrecht C,Symann M

    更新日期:1992-09-01 00:00:00

  • The role of stem cells in aging.

    abstract::The objectives of this review were first to critically review what is known about the effects of aging on stem cells in general, and hematopoietic stem cells in particular. Secondly, evidence is marshalled in support of the hypothesis that aging stem cells play a critical role in determining the effects of aging on or...

    journal_title:Experimental hematology

    pub_type: 杂志文章,评审

    doi:10.1016/s0301-472x(03)00088-2

    authors: Van Zant G,Liang Y

    更新日期:2003-08-01 00:00:00

  • Differential adherence of murine hematopoietic stem cell subsets to fibronectin.

    abstract::Growth and differentiation of hematopoietic stem cells occur in close contact with the cells and extracellular-matrix (ECM) proteins of the hematopoietic microenvironment. We observed the role of fibronectin, a matrix glycoprotein proposed to be involved in the attachment of hematopoietic cells and in the binding of s...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: van der Sluijs JP,Baert MR,Ploemacher RE

    更新日期:1994-12-01 00:00:00

  • Prdm3 and Prdm16 cooperatively maintain hematopoiesis and clonogenic potential.

    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

    authors: McGlynn KA,Sun R,Vonica A,Rudzinskas S,Zhang Y,Perkins AS

    更新日期:2020-05-01 00:00:00

  • Mutagenic and toxic effects of 4-hydroperoxycyclophosphamide and of 2,4-tetrahydrocyclohexylamine (ASTA-Z-7557) on human lymphocytes cultured in vitro.

    abstract::Certain biological effects exerted by 4-hydroperoxycyclophosphamide and by 2,4-tetrahydrocyclohexylamine (ASTA-Z-7557), utilized in vitro in the therapy of leukemias and lymphomas to eliminate the occult tumor cells in autologous marrow transplantations, were studied in human lymphocytes cultured in vitro. The data sh...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: Perocco P,Pane G,Santucci MA,Zannotti M

    更新日期:1985-11-01 00:00:00

  • Comparative influences of phytohemagglutinin-stimulated leukocyte conditioned medium, hemin, prostaglandin E, and low oxygen tension on colony formation by erythroid progenitor cells in normal human bone marrow.

    abstract::The comparative influences of phytohemagglutinin-stimulated leukocyte conditioned medium (PHALCM), hemin, prostaglandin E1 (PGE1), and growth of cells at low oxygen tension (5% O2) were evaluated for their capacity to enhance colony formation in vitro from normal human bone marrow erythroid progenitor cells (BFU-E). E...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: Lu L,Broxmeyer HE

    更新日期:1985-11-01 00:00:00

  • Thyroid hormones enhance hypoxia-induced erythropoietin production in vitro.

    abstract::Effects of thyroid hormones on the production of erythropoietin (Epo) were investigated in isolated perfused rat kidneys and in the human hepatoma cell line, HepG2. Epo protein was measured by radioimmunoassay. L-triiodothyronine and L-thyroxine stimulated hypoxia-induced Epo formation both in the kidney and in HepG2 ...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: Fandrey J,Pagel H,Frede S,Wolff M,Jelkmann W

    更新日期:1994-03-01 00:00:00

  • Intra-bone marrow injection of bone marrow and cord blood cells: an alternative way of transplantation associated with a higher seeding efficiency.

    abstract:OBJECTIVE:Intravenous (IV) injection is currently the normal method for transplanting hematopoietic cells. However, the problem of seeding efficiency and homing is relevant especially when a limited number of stem cells is available. Intra-bone marrow (IBM) injection of bone marrow cells (BMCs) may overcome this proble...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/j.exphem.2004.05.026

    authors: Castello S,Podestà M,Menditto VG,Ibatici A,Pitto A,Figari O,Scarpati D,Magrassi L,Bacigalupo A,Piaggio G,Frassoni F

    更新日期:2004-08-01 00:00:00

  • Targeting cell-bound MUC1 on myelomonocytic, monocytic leukemias and phenotypically defined leukemic stem cells with anti-SEA module antibodies.

    abstract::Cell surface molecules aberrantly expressed or overexpressed by myeloid leukemic cells represent potential disease-specific therapeutic targets for antibodies. MUC1 is a polymorphic glycoprotein, the cleavage of which yields two unequal chains: a large extracellular α subunit containing a tandem repeat array bound in ...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/j.exphem.2018.12.002

    authors: Guillaume T,Dehame V,Chevallier P,Peterlin P,Garnier A,Grégoire M,Pichinuk E,Rubinstein DB,Wreschner DH

    更新日期:2019-02-01 00:00:00

  • CBP/Catenin antagonists: Targeting LSCs' Achilles heel.

    abstract::Cancer stem cells (CSCs), including leukemia stem cells (LSCs), exhibit self-renewal capacity and differentiation potential and have the capacity to maintain or renew and propagate a tumor/leukemia. The initial isolation of CSCs/LSCs was in adult myelogenous leukemia, although more recently, the existence of CSCs in a...

    journal_title:Experimental hematology

    pub_type: 杂志文章,评审

    doi:10.1016/j.exphem.2017.04.010

    authors: Kim YM,Gang EJ,Kahn M

    更新日期:2017-08-01 00:00:00

  • Growth inhibitory effect of gene-cloned interferons on human myeloblast colonies.

    abstract::The effect on marrow myeloblast colony formation in blood from nine patients with acute myeloid leukemia was studied by using three recombinant-DNA-derived human leukocyte interferons (IFN alpha 2, IFN alpha-A, and IFN alpha-C). In preliminary experiments, a brief exposure of leukemic marrow cells to IFN alpha resulte...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: Freedman MH,Fish E,Estrov Z,Grunberger T,Williams BR

    更新日期:1985-10-01 00:00:00

  • Effect of circadian variation on neutrophil mobilization to the peripheral blood in benign constitutional neutropenia.

    abstract::Benign constitutional neutropenia (BCN) is an asymptomatic condition characterized by mild chronic neutropenia in patients with no history of recurrent infections. Most patients are referred for further testing, increasing health care costs. We present an alternative form of assessment of individuals with BCN based on...

    journal_title:Experimental hematology

    pub_type: 临床试验,杂志文章

    doi:10.1016/j.exphem.2018.10.007

    authors: Souto Filho JTD,Portugal RD,Nucci M

    更新日期:2019-01-01 00:00:00

  • Lack of genetic damage in mammalian cells after cryopreservation at -196 degrees C.

    abstract::Mammalian tissue culture cells when cryopreserved according to standard procedures do not show gross chromosomal changes as evidenced by the formation of micronuclei. Cryoprotective agents used in this study included dimethyl sulfoxide (DMSO), glycerol and polyvinylpyrollidone (PVP) in combination with serum and using...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: Ashwood-Smith MJ

    更新日期:1979-01-01 00:00:00

  • T-cell P/E-selectin ligand alpha(1,3)fucosylation is not required for graft-vs-host disease induction.

    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

    authors: Eom HS,Rubio MT,Means TK,Luster AD,Sykes M

    更新日期:2005-12-01 00:00:00

  • Ectopic implantation studies using Sl/Sld marrow and recipients.

    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:

    authors: Schofield R,Lorimore SA,Wright EG

    更新日期:1987-03-01 00:00:00

  • Recovery of hematologic competence without engraftment following attempted bone marrow transplantation for aplastic anemia: Report of a case with diffusion chamber studies.

    abstract::An 18-year-old male with severe aplastic anemia associated with hepatitis was prepared for bone marrow transplantation with cyclophosphamide (50 mg/kg/day) for 4 consecutive days. He then received 3.47 X 10(8) nucleated bone marrow cells per kilogram of body weight from his HL-A identical sister by intravenous infusio...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: Sensenbrenner LL,Steele AA,Santos GW

    更新日期:1977-01-01 00:00:00

  • Regulation of the functional activity of mast cells and fibroblasts by mononuclear cells in murine and human chronic graft-vs.-host disease.

    abstract::Mast cell (MC)-fibroblast-immunocompetent cell interactions may play a role in the inflammatory and fibrotic processes present in chronic graft-vs.-host disease (cGVHD). Interactions between these cell types were examined in both murine and human cGVHD models. To this purpose, cell supernatants from mice or humans wit...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: Levi-Schaffer F,Segal V,Barak V,Rubinchik E,Nagler A

    更新日期:1997-03-01 00:00:00

  • Tolerance in DLA-haploidentical canine littermates following CD6-depleted marrow transplantation and donor lymphocyte transfusion.

    abstract:OBJECTIVE:Donor lymphocyte transfusions (DLT) are effective in the treatment of leukemia after allogeneic stem cell transplantation. Graft-vs-host-disease (GVHD) is the major risk factor of DLT. In dog leukocyte antigen (DLA)-identical littermate dogs, DLT given within 3 weeks after transplantation of marrow depleted o...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/j.exphem.2009.05.001

    authors: Zorn J,Herber M,Schwamberger S,Panzer W,Adler H,Kolb HJ

    更新日期:2009-08-01 00:00:00