Abstract：
:Myelodysplastic syndromes (MDSs) are clonal disorders of hematopoietic stem and progenitor cells and represent the most common cause of acquired marrow failure. Hallmarked by ineffective hematopoiesis, dysplastic marrow, and risk of transformation to acute leukemia, MDS remains a poorly treated disease. Although identification of hematopoietic aberrations in human MDS has contributed significantly to our understanding of MDS pathogenesis, evidence now identify the bone marrow microenvironment (BMME) as another key contributor to disease initiation and progression. With improved understanding of the BMME, we are beginning to refine the role of the hematopoietic niche in MDS. Despite genetic diversity in MDS, interaction between MDS and the BMME appears to be a common disease feature and therefore represents an appealing therapeutic target. Further understanding of the interdependent relationship between MDS and its niche is needed to delineate the mechanisms underlying hematopoietic failure and how the microenvironment can be targeted clinically. This review provides an overview of data from human MDS and murine models supporting a role for BMME dysfunction at several steps of disease pathogenesis. Although no models or human studies so far have combined all of these findings, we review current data identifying BMME involvement in each step of MDS pathogenesis organized to reflect the chronology of BMME contribution as the normal hematopoietic system becomes myelodysplastic and MDS progresses to marrow failure and transformation. Although microenvironmental heterogeneity and dysfunction certainly add complexity to this syndrome, data are already demonstrating that targeting microenvironmental signals may represent novel therapeutic strategies for MDS treatment.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Li AJ,Calvi LMdoi
10.1016/j.exphem.2017.08.003subject
Has Abstractpub_date
2017-11-01 00:00:00pages
3-18eissn
0301-472Xissn
1873-2399pii
S0301-472X(17)30718-Xjournal_volume
55pub_type
杂志文章,评审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：:Infection of splenectomized mice with Diplococcus pneumoniae, type III, resulted in a fourfold higher mortality rate than did infection of normal mice. Splenectomized animals were protected against fulminant, fatal sepsis by subcutaneous transplantation of autochthonous splenic tissue at the time of splenectomy. Anima...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1978-05-01 00:00:00
abstract：:After initially successful chemotherapy, relapse frequently jeopardizes the outcome of patients with acute leukemia. Because of their adverse characteristics of self-renewal and dormancy, leukemia stem cells have been hypothesized to play a critical role in resistance to antiproliferative chemotherapy and the developm...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2018.09.006
更新日期：2019-01-01 00:00:00
abstract：:The effects of the inhibition of the cyclooxygenase and lipoxygenase metabolic pathways of arachidonic acid on the postirradiation recovery of hematopoietic functions in mice were investigated. Nordihydroguaiaretic acid (NDGA), an inhibitor of prostaglandin (PG) and leukotriene (LT) production, was given to animals in...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-01-01 00:00:00
abstract：:The synthesis and expression of protein complexes of 23,000 and 30,00 dalton (p23,30) HLA-DR antigen, and of 44,000 and 12,000 dalton (p44,12) HLA-A,B antigen and beta 2-microglobulin was demonstrated on human peripheral blood monocytes and in cultures of purified, adherent monocytes. In indirect immunofluorescence as...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-07-01 00:00:00
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
更新日期：2007-06-01 00:00:00
abstract：OBJECTIVE:Morbidity and mortality occurring in patients with multiple myeloma, AL amyloidosis, and light chain deposition disease can result from the pathologic deposition of monoclonal immunoglobulin light chains (LCs) in kidneys and other organs. To reduce synthesis of such components, therapy for these disorders typ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2010.07.001
更新日期：2010-11-01 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：:Similarly to other tissues, the bone marrow contains subsets of resident tissue macrophages, which are essential to maintain bone formation, functional hematopoietic stem cell (HSC) niches, and erythropoiesis. Pharmacologic doses of granulocyte colony-stimulating factor (G-CSF) mobilize HSC in part by interfering with...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2014.03.009
更新日期：2014-07-01 00:00:00
abstract：:The hematologic effects of recombinant human interleukin-6 (rhIL-6) were studied in dogs exposed to a total-body irradiation (TBI) of 2.4 Gy. IL-6 was administered over a period of 14 days at a daily dose of 18 micrograms/kg by single subcutaneous injection. Treatment was started 1 day after TBI. The data obtained for...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1994-07-01 00:00:00
abstract：:Neutropenia is common to both Hermansky-Pudlak syndrome type 2 and canine cyclic hematopoiesis (CH) which are caused by mutations in the AP3B1 gene. The purpose of this study was to determine if pearl mice were neutropenic. Complete blood counts (CBCs) and bone marrow differential counts, colony forming unit (CFU) ass...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2013.05.002
更新日期：2013-10-01 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：:The relative contributions of various organs to platelet production is controversial. In this study, serial histologic sections of bone marrow, spleen, liver, and lung from normal C57BL/6J mice and mice that had received three different agents which perturb normal murine thrombopoiesis (platelet antiserum, 5-fluoroura...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1997-07-01 00:00:00
abstract：OBJECTIVE:We previously demonstrated the presence of nucleoside diphosphate kinase NDPK/NM23 in normal human plasma. It also was reported that extracellular NM23 could inhibit differentiation of certain hematopoietic cell lines. We further investigated the extracellular effect of NM23 on hematopoiesis by adding recombi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00809-3
更新日期：2002-07-01 00:00:00
abstract：:We have found that treatment of B6SUtA1 cells with 0.01% glutaraldehyde transformed them into mechanically resistant spheres, thereby making it possible to use these high interleukin 3 (IL-3) receptor-bearing cells as a solid phase reagent suitable for the large scale purification of murine IL-3 (mIL-3). Using this te...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-11-01 00:00:00
abstract：:Murine low-density bone marrow cells sorted from the blast cell window on the basis of high rhodamine-123 retention (Rh-bright), are highly enriched in histamine-, IL-4-, and IL-6-producing cells. We established by in situ hybridization that up to 50% of this population (around 0.25% of the whole bone marrow) coexpres...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(99)00039-9
更新日期：1999-06-01 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：OBJECTIVE:It has been shown previously that infection with diverse viruses induces alterations in bone marrow lineage-specific progenitor cells. As complications arising from secondary bacterial infections can adversely affect the host, we investigated whether virally induced hematological alterations could contribute ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2005.09.005
更新日期：2005-12-01 00:00:00
abstract：:A useful cytochemical technique has been developed which facilitates the identification of the types of cell aggregates which proliferate in soft agar cultures of hematopoietic stem cells. Staining of fixed agar discs for alpha-naphthyl acetate esterase (ANAE), naphthol AS-D chloroacetate esterase (CAE) and with Luxol...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1983-01-01 00:00:00
abstract：:We examined the effect of vesnarinone, an oral cardiotonic, on the growth and differentiation of human myeloid leukemia cells. Vesnarinone alone markedly induced erythroid differentiation of HEL cells. All-trans-retinoic acid also induced erythroid differentiation of the cells, and the differentiation was greatly enha...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1996-01-01 00:00:00
abstract：:Clonality studies can establish the single-cell origin of tumors and thus differentiate clonal malignant and premalignant processes from reactive polyclonal processes. Detection of clonal cells may be based on direct tracking of cell lineage-specific sequences or disease-specific somatic mutations identifying the clon...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2020.01.013
更新日期：2020-03-01 00:00:00
abstract：OBJECTIVE:Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is expressed by the malignant cells of about 30% of cases of Hodgkin's lymphoma (HL) and is therefore a potential target for immune attack. Given the predominantly immunosuppressive nature of HL infiltrating lymphocytes (HLILs) and the ability ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.01.030
更新日期：2007-04-01 00:00:00
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：
更新日期：1979-01-01 00:00:00
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
更新日期：2009-02-01 00:00:00
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
更新日期：2009-01-01 00:00:00
abstract：OBJECTIVE:The function of neutrophils as primary mediators of innate immunity depends on the activity of granule proteins and critical components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Expression of their cognate genes is regulated during neutrophil differentiation by a complex netw...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.02.009
更新日期：2008-07-01 00:00:00
abstract：:The mechanism of localization, migration, and regulation of hematopoiesis at different stages of ontogeny is not well understood, but may relate to the specific adhesive interactions between hematopoietic stem cells and their microenvironment at different ontogenic stages. We studied the expression of cell adhesion mo...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(98)00031-9
更新日期：1999-02-01 00:00:00
abstract：OBJECTIVE:Regulation of the cell cycle by cyclin-dependent kinase (CDK) activity occurs at multiple levels and is often altered in human cancers. Therefore, CDK activity has been targeted for drug discovery, and a number of small molecules have now been identified as CDK inhibitors. Plant cytokinin analogues with CDK i...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00894-9
更新日期：2002-10-01 00:00:00
abstract：OBJECTIVE:The aim of this study was to evaluate the occurrence of T-cell spontaneous apoptosis (A(spont)) and its modulation in vitro by the interleukin-2 receptor (IL-2R) gamma-chain (gammac)-signaling cytokine IL-15 in patients transplanted with autologous peripheral blood progenitor cells (PBPC) for hematologic mali...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(01)00747-0
更新日期：2001-12-01 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
