Abstract:
:Histone deacetylase inhibitors (HDACIs) have demonstrated effectiveness against lymphomas and myelomas in clinical practice. However, common to all currently approved broad-acting HDACIs (panHDACIs) is dose-limiting thrombocytopenia, which has prevented wider use in cancer therapy. Using CD34+ hematopoietic stem cells (HSCs), we show that megakaryocyte (MK) cell maturation and differentiation are impaired by panHDACIs, correlating to clinical thrombocytopenia. Importantly, we demonstrate that inhibitors of class II histone deacetylases (HDACs), including LMK235 and tubacin at clinically relevant concentrations, do not affect MK maturation. Furthermore, we show that HDACI-induced impairment of MK differentiation is associated with reduction of protein levels of the transcription factor GATA-1, but not tubulin hyperacetylation. Finally, we report that panHDACIs trigger a rapid loss of GATA-1 protein via a proteasome-dependent pathway. Our data support the notion that specifically targeting class II HDACs in cancer treatment is a potential strategy that would offer a safer alternative than current panHDACIs.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Simic D,Sang Ndoi
10.1016/j.exphem.2018.12.007subject
Has Abstractpub_date
2019-04-01 00:00:00pages
36-46eissn
0301-472Xissn
1873-2399pii
S0301-472X(19)30005-0journal_volume
72pub_type
杂志文章abstract:OBJECTIVE:Nonmyeloablative conditioning regimens for marrow transplantation are desirable in many settings. Because repeated doses of the antimetabolite 5-fluorouracil (5-FU) decreases marrow long-term repopulating ability (LTRA) upon transplantation into lethally irradiated hosts, we hypothesized that mice given seque...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.08.007
更新日期:2004-12-01 00:00:00
abstract:OBJECTIVE:For approximately 5% of autologous transplant recipients and a higher proportion of allogeneic transplant recipients, low level and delayed platelet engraftment is an ongoing problem. Mesenchymal stem cells (MSC), which can be derived from bone marrow as well as other organs, are capable of differentiation in...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(03)00042-0
更新日期:2003-05-01 00:00:00
abstract::Previous studies have suggested that Steel factor (SF) can influence the behavior of many types of hematopoietic progenitor cells both in vivo and in vitro, although whether these may include the most primitive populations of totipotent repopulating cells remains controversial. To approach this question, we measured t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-02-01 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::The circadian and circannual rhythms of committed stem cells (CFUc) were investigated by using the agar colony technique. There was a marked circadian rhythmicity, with variations between maximum and minimum colony yields of 2-5.5 times; such variations could also be seen throughout the year. A phase shift was observe...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract:OBJECTIVE:Preservation of hematopoietic stem and progenitor cells from early radiation-induced apoptosis is the rationale for emergency antiapoptotic cytokine therapy (EACK) after radiation accidents. This strategy is based on the combination of stem cell factor + Flt3-ligand + thrombopoietin + interleukin 3 (SFT3). Th...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.04.017
更新日期:2007-08-01 00:00:00
abstract::We compared the effects of recombinant (r) tumor necrosis factor (TNF) and lymphotoxin (rLT) on in vitro colony formation by erythroid, multipotential and granulocyte, monocyte (CFU-GM) precursor cells. Recombinant granulocyte, macrophage-colony stimulating factor and bone marrow preparations enriched for hematopoieti...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-02-01 00:00:00
abstract:OBJECTIVE:Multipotent germline stem (mGS) cells derived from neonatal mouse testis, similar to embryonic stem (ES) cells, differentiate into various types of somatic cells in vitro and produce teratomas after inoculation into mice. In the present work, we examined mGS cells for hematopoietic progenitor potential in vit...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.09.006
更新日期:2009-12-01 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::The anemia of Belgrade b/b rats has been shown to be due to intracellular iron deficiency. The aim of this study of erythropoiesis at the progenitor cell level in these rats was to determine if a defect is present in the early phase of red cell production. Both erythroid colony-forming unit (CFU-E)- and erythroid burs...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-08-01 00:00:00
abstract:OBJECTIVE:MicroRNAs (miRNAs) are an abundant class of small noncoding RNAs that regulate diverse cellular functions by sequence-specific inhibition of gene expression. We determined miRNA expression profile during erythroid differentiation and putative roles in erythroid differentiation. METHODS:The expression profile...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.03.014
更新日期:2007-07-01 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::Umbilical cord blood (CB) is a rich source of hematopoietic stem cells (HSCs) with important applications in allogeneic stem cell transplantation. However, the low numbers of hematopoietic stem and progenitor cells (HSPCs) in banked units remain a major limitation. Protocols developed for HSPC expansion ex vivo or to ...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2015.04.011
更新日期:2015-07-01 00:00:00
abstract:OBJECTIVE:Graft-versus-leukemia effects of donor lymphocytes have been considered to be central to the therapeutic benefit of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) for malignant diseases. Surprisingly, some patients who reject donor grafts following nonmyeloablative HCT have sustained rem...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.04.022
更新日期:2006-09-01 00:00:00
abstract::We compared the kinetic recovery of lymphocytes and their subsets in two groups of patients submitted to allogeneic peripheral blood progenitor cell transplantation (allo-PBT): those receiving lymphocyte-depleted leukaphereses by positive selection of CD34+ cells (group 1, n = 18) and those receiving unmanipulated leu...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(98)00029-0
更新日期:1999-03-01 00:00:00
abstract::Leukemic monoblasts obtained from three children were evaluated for their in vitro physiologic characteristics. These monoblasts were alpha naphthyl acetate esterase positive, exhibited glass adherence, had IgG membrane receptors, phagocytized latex particles with subsequent nitroblue tetrazolium (NBT) reduction, and ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-01-01 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::A novel polypeptide with a molecular weight of 17 kd (17k protein) was identified in bone marrow cell cultures. The synthesis of 17k protein is elevated in cell cultures maintained under Dexter conditions, which support myelopoiesis. The predominance of macrophages in the stromal layer of these cultures and the observ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-10-01 00:00:00
abstract::The heterogeneity among progenitor cells of granulocytes and macrophages capable of forming colonies in vitro (CFU-c) is analysed. If specific culture conditions and stimuli are used, it is possible to discriminate among three subpopulations of CFU-c. CFU-c directly responding to CSF prepared from pregnant mouse uteri...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1979-11-01 00:00:00
abstract:OBJECTIVE:Assays that can evaluate the potential of individual human hematopoietic stem cells (HSC) are still lacking. We previously developed the myeloid-lymphoid initiating cell (ML-IC) assay that enumerates single CD34(+) cells that generate long-term culture-initiating (LTC-IC) and NK-initiating (NK-IC) daughter ce...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.10.016
更新日期:2005-02-01 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:OBJECTIVES:To identify the regulatory sequences driving Gata1 expression in conventional dendritic cells (cDC). MATERIALS AND METHODS:The number and expression levels of Gata1, Gata1-target genes and hypersensitive site (HS) 2 (the eosinophil-specific enhancer)-driven green fluorescent protein (GFP) reporter of cDCs f...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.03.006
更新日期:2010-06-01 00:00:00
abstract::We have examined the capacity of highly purified human CD34+ marrow cell isolates from unrelated, HLA-mismatched donors to establish in vitro hematopoiesis on recipient marrow stromal cells in 2-stage hematopoietic long-term marrow cultures (H-LTMC). HLA-typing of both peripheral blood mononuclear cells and CD34+ marr...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-11-01 00:00:00
abstract::Previous systems for cloning human T-cells have been either one step procedures with small colony size (40 less than 40 cells) or two-step procedures with agglutination problems. These systems also require erythrocytes, thiols and human serum. We have regularly grown more than 10(3) colonies (more than 40 cells)/5 X 1...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-11-01 00:00:00
abstract:OBJECTIVE:Hematopoietic progenitor cells are a promising source for generation of genetically modified dendritic cells. A prerequisite for using these cells in therapeutic approaches is stable vector-mediated transgene expression during and after cell maturation. We investigated the expression of enhanced green fluores...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00778-0
更新日期:2002-02-01 00:00:00
abstract::A cell line (LAMA-84) has been established from the blood of a patient with chronic myeloid leukemia in acute phase. LAMA-84 cells retained the patient's chromosome abnormalities, i.e., triplication of all chromosomes except chromosome 18, the presence of Philadelphia (Ph) chromosome in 4-5 copies, and the presence of...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-09-01 00:00:00
abstract::Arsenic trioxide (As2O3) has been demonstrated to be effective for the treatment of acute promyelocytic leukemia (APL) and to inhibit proliferation and produce apoptosis in the APL cell line NB4. To determine if As2O3 might be useful for the treatment of other lineages, we investigated the effects of As2O3 on viabilit...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(99)00014-4
更新日期:1999-05-01 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:OBJECTIVE:We have previously shown that nitric oxide (NO) is involved in the hydroxyurea-induced increase of gamma-globin gene expression in cultured human erythroid progenitor cells and that hydroxyurea increases NO production in endothelial cells via endothelial NO synthase (NOS). We have now expanded those studies t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.06.009
更新日期:2009-10-01 00:00:00
abstract::Graft-versus-host disease (GVHD), mediated by donor-derived alloreactive T cells, is a major cause of nonrelapse mortality in allogeneic hematopoietic stem cell transplantation. Its therapy is not well-defined. We established allele-specific anti-human leukocyte antigen (HLA) monoclonal antibodies (ASHmAbs) that speci...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2014.10.008
更新日期:2015-02-01 00:00:00