Characterization of defective megakaryocytic development in patients with myelodysplastic syndromes.

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]). Bone marrow-derived CD34+ cells were enriched to a purity of 87% +/- 2% (mean +/- SEM) and assayed in short-term suspension cultures in the presence of 10 ng/mL of PEGylated recombinant human megakaryocyte (MK) growth and development factor (PEG-rHuMGDF) and in addition to 50 ng/mL stem cell factor and 10 ng/mL interleukin-3. Cells of the megakaryocytic lineage were identified by flow cytometric analysis of CD42b (GP1b) and mature MKs by morphologic criteria. Transcription of c-mpl receptor-specific mRNA in the CD34+ cells of these patients was investigated by full-length reverse transcriptase polymerase chain reaction of the p form of c-mpl as well as of the alternative splice product c-mpl k. CD34+ cells from seven healthy bone marrow donors served as controls. Differentiation along the MK pathway was stimulated in five patients with RA. C-mpl mRNA was expressed in the CD34+ cells in all cases. In three low-risk patients the capacity for in vitro MK growth was absent or minimal even though mRNA for c-mpl receptor was detected in the CD34+ cells of this group as well. In patients with high-risk MDS, PEG-rHuMGDF stimulated in vitro MK growth from CD34+ cells in only one of five cases. As in the patients with low-risk MDS, c-mpl mRNA for both c-mpl p and c-mpl k splicing products was detected. These results indicate that the in vitro response to stimulation with c-mpl ligand discriminates between two groups of patients with low-risk MDS and that the observed defect in megakaryocytic development is unrelated to the level of c-mpl expression in both low-risk and high-risk MDS.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

Hofmann WK,Kalina U,Wagner S,Seipelt G,Ries C,Hoelzer D,Ottmann OG

doi

10.1016/s0301-472x(98)00077-0

keywords:

subject

Has Abstract

pub_date

1999-03-01 00:00:00

pages

395-400

issue

3

eissn

0301-472X

issn

1873-2399

pii

S0301-472X(98)00077-0

journal_volume

27

pub_type

杂志文章
  • Differential engraftment of genetically modified CD34(+) and CD34(-) hematopoietic cell subsets in lethally irradiated baboons.

    abstract:OBJECTIVE:To test gibbon ape leukemia virus (GALV) pseudotype vector transduction of marrow subpopulations that contribute to hematopoietic reconstitution in vivo. MATERIALS AND METHODS:Autologous CD34(+) Lin(-), CD34(+) Lin(+), and CD34(-) Lin(-) marrow cells, transduced by coculture with PG13/LN, PG13/LNX, and PG13/...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/s0301-472x(00)00137-5

    authors: Andrews RG,Peterson LJ,Morris J,Potter J,Heyward S,Gough M,Bryant E,Kiem HP

    更新日期:2000-05-01 00:00:00

  • Contribution of STAT3 to the activation of survivin by GM-CSF in CD34+ cell lines.

    abstract:OBJECTIVE:Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to specifically stimulate proliferation of CD34(+) hematopoietic progenitor cells. Although signal transducers and activators of transcription 3 (STAT3) is believed essential for transduction of GM-CSF-induced cell proliferation, the sig...

    journal_title:Experimental hematology

    pub_type: 临床试验,杂志文章

    doi:10.1016/j.exphem.2007.03.007

    authors: Gu L,Chiang KY,Zhu N,Findley HW,Zhou M

    更新日期:2007-06-01 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

  • Mode of action of erythropoietin (Epo) in an Epo-dependent murine cell line. II. Cell cycle dependency of Epo action.

    abstract::Erythropoietin (Epo), a glycoprotein hormone, regulates the proliferation and differentiation of committed erythroid progenitor cells. We investigated the effect of Epo on the kinetics of an Epo-dependent cell line (DA-1ER), which was cloned from the murine interleukin 3-dependent cell line, DA-1. Flow cytometry and [...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: Tsuda H,Sawada T,Kawakita M,Takatsuki K

    更新日期:1989-03-01 00:00:00

  • Effect of 1,25 dihydroxyvitamin D3 and retinoic acid on normal human pluripotent (CFU-mix), erythroid (BFU-E), and myeloid (CFU-C) progenitor cell growth and differentiation patterns.

    abstract::The modulatory effect of 1,25 dihydroxyvitamin D3 (vit D) and 13 cis retinoic acid (retinoic acid) on the growth and differentiation of normal human pluripotent stem cell, erythroid, and myeloid progenitor cell growth was studied using semisolid methylcellulose clonal assay. Dose response curves showed that maximal in...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: Nagler A,Riklis I,Kletter Y,Tatarsky I,Fabian I

    更新日期:1986-01-01 00:00:00

  • Arid2 regulates hematopoietic stem cell differentiation in normal hematopoiesis.

    abstract::The switch/sugar nonfermenting (SWI/SNF) family of chromatin remodeling complexes have been implicated in normal hematopoiesis. The ARID2 protein is a component of the polybromo-associated BAF (PBAF), one of the two main SWI/SNF complexes. In the current study, we used a conditional Arid2 knockout mouse model to deter...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/j.exphem.2020.12.004

    authors: Bluemn T,Schmitz J,Chen Y,Zheng Y,Zhang Y,Zheng S,Burns R,DeJong J,Christiansen L,Izaguirre-Carbonell J,Wang D,Zhu N

    更新日期:2020-12-17 00:00:00

  • Prospective identification of erythroid elements in cultured peripheral blood.

    abstract::We have developed a prospective approach to identify the generation of erythroid cells derived from cultured peripheral blood mononuclear cells (PBMC) by monitoring the expression of the cell surface protein CD48. Unpurified populations of PBMC obtained from the buffy coats of normal volunteers were grown in suspensio...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/s0301-472x(98)00086-1

    authors: Miller JL,Njoroge JM,Gubin AN,Rodgers GP

    更新日期:1999-04-01 00:00:00

  • Reduced expression of flavocytochrome b558, a component of the NADPH oxidase complex, in neutrophils from patients with myelodysplasia.

    abstract:OBJECTIVE:Patients with myelodysplasia (MDS) show a disturbed production of ROS in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) in granulocyte-macrophage colony-stimulating factor (GM-CSF)-primed neutrophils. Because generation of ROS is mediated by the NADPH oxidase complex, a component of which is...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/s0301-472x(03)00188-7

    authors: Fuhler GM,Hooijenga F,Drayer AL,Vellenga E

    更新日期:2003-09-01 00:00:00

  • The problem of toxicity in the bioassay for erythropoietin using mouse fetal liver cells.

    abstract::The use of neonatal instead of fetal calf serum, as a constituent of the culture medium, confronted the authors with the problem of toxicity in the fetal liver cell erythropoietin assay. Tested human sera were toxic at rather low concentrations. Heating the human sera for 30 min at 56 degrees C abolished the toxicity....

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: von Preyss B,Goudsmit R

    更新日期:1976-05-01 00:00:00

  • Proliferation of single hemopoietic progenitor cells in the absence of colony-stimulating factors and serum.

    abstract::The proliferative capacity of partially purified populations of mouse bone marrow progenitor cells has been examined in serum-free cultures in the presence and absence of colony-stimulating factors (CSFs). The half-life of progenitor cells was approximately 25 h in the absence of factor, regardless of whether the fact...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: Péléraux A,Eliason JF

    更新日期:1989-11-01 00:00:00

  • Mesodermal patterning activity of SCL.

    abstract::The transcription factor SCL is critically required for establishing hematopoiesis and for proper endothelial development, but not for maintenance of hematopoietic stem cells or endothelial cells in the adult. Conflicting data exists regarding the developmental function of SCL, namely, whether it acts as a master regu...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/j.exphem.2008.07.005

    authors: Ismailoglu I,Yeamans G,Daley GQ,Perlingeiro RC,Kyba M

    更新日期:2008-12-01 00:00:00

  • Kinetics of lentiviral vector transduction in human CD34(+) cells.

    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

    authors: Uchida N,Green R,Ballantine J,Skala LP,Hsieh MM,Tisdale JF

    更新日期:2016-02-01 00:00:00

  • Bone marrow-derived endothelial progenitor cells do not contribute significantly to new vessels during incisional wound healing.

    abstract:OBJECTIVE:To assess the contribution of bone marrow (BM)-derived endothelial progenitor cells (EPCs) to the neovascularisation of cutaneous incisional wounds. METHODS:Lethally irradiated C57Bl/6 mice were transplanted with BM mononuclear cells from Tie2/lacZ mice, which constitutively overexpressed beta-galactosidase ...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/j.exphem.2006.10.016

    authors: Bluff JE,Ferguson MW,O'Kane S,Ireland G

    更新日期:2007-03-01 00:00:00

  • Inhibitory effects of HIV-1-infected stromal cell layers on the production of myeloid progenitor cells in human long-term bone marrow cultures.

    abstract::This report presents the results of studies using long-term bone marrow cultures (LTBMC) of human bone marrow cells to investigate the effect of HIV-1 on in vitro hematopoiesis. Confluent stromal cell layers established from human bone marrow cells were irradiated to eliminate residual hematopoietic progenitor cells a...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: Schwartz GN,Kessler SW,Rothwell SW,Burrell LM,Reid TJ,Meltzer MS,Wright DG

    更新日期:1994-12-01 00:00:00

  • Induction of differentiation of human myeloid leukemia cells by immunosuppressant macrolides (rapamycin and FK506) and calcium/calmodulin-dependent kinase inhibitors.

    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

    authors: Yamamoto-Yamaguchi Y,Okabe-Kado J,Kasukabe T,Honma Y

    更新日期:2001-05-01 00:00:00

  • Induced pluripotent stem cell modeling of malignant hematopoiesis.

    abstract::The ability to epigenetically reprogram differentiated somatic cells to pluripotency resulting in the discovery of induced pluripotent stem cells (iPSCs), has unlocked fundamental biologic insights into numerous genetic diseases. These insights have resulted from the key property of iPSCs to differentiate into all cel...

    journal_title:Experimental hematology

    pub_type: 杂志文章,评审

    doi:10.1016/j.exphem.2019.01.002

    authors: Chao MP,Majeti R

    更新日期:2019-03-01 00:00:00

  • Multilineage dysplasia as assessed by immunophenotype has no impact on clinical-biological features and outcome of NPM1-mutated acute myeloid leukemia.

    abstract::The presence of multilineage dysplasia (MLD) by morphology at diagnosis in acute myeloid leukemia (AML) defines a separate subset in the World Health Organization classification with still-debated prognostic value. A major controversy concerns MLD's role in NPM1-mutated (NPM1⁺) AML, which correlates with good prognosi...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/j.exphem.2015.06.003

    authors: Mannelli F,Ponziani V,Bonetti MI,Bencini S,Cutini I,Gianfaldoni G,Scappini B,Pancani F,Rondelli T,Benelli M,Caporale R,Grazia Gelli AM,Peruzzi B,Longo G,Bosi A

    更新日期:2015-10-01 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

  • Indomethacin augments granulocyte-macrophage colony-stimulating factor-induced hematopoiesis following 5-FU treatment.

    abstract::We have previously reported that granulocyte-macrophage colony-stimulating factor (GM-CSF) given after the administration of 5-fluorouracil (5-FU) results in augmented hematopoietic recovery as evidenced by increased white blood cell and neutrophil counts. Mice receiving GM-CSF following 5-FU administration were obser...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: O'Reilly M,Gamelli RL

    更新日期:1990-10-01 00:00:00

  • Podocalyxin selectively marks erythroid-committed progenitors during anemic stress but is dispensable for efficient recovery.

    abstract:OBJECTIVE:Podocalyxin expression on Ter119(+) erythroblasts is induced following administration of erythropoietin (Epo) or phenylhydrazine treatment, but is notably absent on committed erythroid progenitors during homeostatic red cell turnover. Following high-dose Epo administration in vivo, podocalyxin surface express...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/j.exphem.2008.09.006

    authors: Maltby S,Hughes MR,Zbytnuik L,Paulson RF,McNagny KM

    更新日期:2009-01-01 00:00:00

  • Effects of estrogen on hepatic hemopoiesis in the adult mouse.

    abstract::After a single pharmacologic dose of estriol (E3) treatment, an increase in number of focal areas of hepatic hemopoiesis was observed in adult mice. When syngeneic bone marrow cells were transfused into E3-treated mice, focal hepatic hemopoiesis was increased further. In a single experiment, using a single cell suspen...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: Hayama T,Nawa Y,Ezaki T,Kotani M

    更新日期:1983-08-01 00:00:00

  • Canine platelet von Willebrand factor: quantification and multimeric analysis.

    abstract::Washed canine platelets were shown to express a significant level of von Willebrand factor (vWf). Canine platelet vWf differed from canine plasma vWf by the absence of satellite bands associated with each multimer when resolved by SDS-agarose gel electrophoresis. Expression and multimeric composition of canine platele...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: McCarroll DR,Waters DC,Steidley KR,Clift R,McDonald TP

    更新日期:1988-12-01 00:00:00

  • The SCL 3' enhancer responds to Hedgehog signaling during hemangioblast specification.

    abstract:OBJECTIVE:The Hedgehog family of intercellular proteins has a crucial role in embryonic development. Recent experimental data suggests that the Hedgehog pathway may play a role in early hematopoiesis and angiogenesis. Stem cell leukemia (SCL), a basic helix-loop-helix (bHLH) transcription factor, is essential for the s...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/j.exphem.2006.07.019

    authors: Hochman E,Kinston S,Harmelin A,Göttgens B,Izraeli S

    更新日期:2006-12-01 00:00:00

  • Investigations on the pool size, proliferative state and differentiation pattern of splenic CFUC in normal dogs.

    abstract::In the present study we investigated the absolute numbers of granulocytic progenitor cells (CFUc) in the spleens of adult normal dogs, their differentiation pattern and also their proliferative state. Between 10 and 40 times as many CFUc were found in the spleens of individual dogs as were present in the total blood v...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: Nothdurft W,Calvo W,Fliedner TM,Schnappauf HP

    更新日期:1980-09-01 00:00:00

  • Effect of in vitro treatment with indomethacin on mouse granulocyte-macrophage colony-forming cells in culture (CFUC). Possible role of prostaglandins.

    abstract::The effect of indomethacin (6 mg/kg daily orally for 2, 3 or 4 days) on myelopoiesis was studied in mice by estimating 1) differential cell counts of bone marrow, 2) proliferation of the CFUC in presence of GM-CSF, 3) proliferative state of CFUC after tritiated thymidine suicide. After 4 days of treatment, a rise in t...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: Fontagné J,Adolphe M,Semichon M,Zizine L,Lechat P

    更新日期:1980-10-01 00:00:00

  • Fetal hemoglobin induction by histone deacetylase inhibitors involves generation of reactive oxygen species.

    abstract:OBJECTIVE:Several compounds, including butyrate and trichostatin A, have been shown to activate gamma-gene expression via p38 mitogen-activated protein kinase (MAPK) signaling. In eukaryotic cells, reactive oxygen species (ROS) act as signaling molecules to mediate phosphorylation of tyrosine kinases such as p38 MAPK t...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/j.exphem.2005.12.009

    authors: Hsiao CH,Li W,Lou TF,Baliga BS,Pace BS

    更新日期:2006-03-01 00:00:00

  • Human osteosarcoma cell lines MG-63 and SaOS-2 produce G-CSF and GM-CSF: identification and partial characterization of cell-associated isoforms.

    abstract::Bone marrow stem cells reside in close proximity to endosteal osteoblasts. To explore the potential role of osteoblasts in hematopoietic differentiation, we measured the mRNA accumulation, protein production, and secretion of hematopoietic growth factors by the nonmineralizing MG-63 and the mineralizing SaOS-2 human o...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: Taichman RS,Emerson SG

    更新日期:1996-03-01 00:00:00

  • Induction therapy in a multiple myeloma mouse model using a combination of AS101 and melphalan, and the activity of AS101 in a tumor microenvironment model.

    abstract:OBJECTIVE:We previously showed that the organotellurium compound, ammonium trichloro (dioxyethylene-0-0') tellurate (AS101), has antitumoral activity in multiple myeloma (MM) cell lines. Here, we evaluated the antimyeloma activity of AS101 combined with low-dose melphalan, and also examined the activity of AS101 in the...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:10.1016/j.exphem.2009.01.006

    authors: Hayun M,Saida H,Albeck M,Peled A,Haran-Ghera N,Sredni B

    更新日期:2009-05-01 00:00:00

  • Separation of CFU-S from primitive cells responsible for reconstitution of the bone marrow hemopoietic stem cell compartment following irradiation: evidence for a pre-CFU-S cell.

    abstract::We have studied the in vivo spleen colony-forming ability and marrow repopulating ability of murine bone marrow cells differing in mitochondrial activity. Following centrifugal elutriation the cells were sorted on the basis of rhodamine-123 fluorescence intensity within a predetermined light scatter window. It is show...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: Ploemacher RE,Brons RH

    更新日期:1989-03-01 00:00:00

  • Are stem cells exposed to ionizing radiation in vivo as effective as nonirradiated transfused stem cells in restoring hematopoiesis?

    abstract::Are the stem cells that survive graded doses of ionizing radiation as effective in restoring hematopoiesis in irradiated mice as transfused nonirradiated stem cells? This question was addressed by determining animal dose mortality and 10-day colony-forming units (CFU-S) survival curves and then replotting the percent ...

    journal_title:Experimental hematology

    pub_type: 杂志文章

    doi:

    authors: Cronkite EP,Inoue T,Hirabayashi Y,Bullis J

    更新日期:1993-06-01 00:00:00