Abstract:
:Megakaryocytes have been implicated in the micro-environmental abnormalities associated with fibrosis and hematopoietic failure in the bone marrow (BM) of primary myelofibrosis (PMF) patients, the Philadelphia-negative myeloproliferative neoplasm (MPN) associated with the poorest prognosis. To identify possible therapeutic targets for restoring BM functions in PMF, we compared the expression profiling of PMF BM with that of BM from essential thrombocytopenia (ET), a fibrosis-free MPN also associated with BM megakaryocyte hyperplasia. The signature of PMF BM was also compared with published signatures associated with liver and lung fibrosis. Gene set enrichment analysis (GSEA) identified distinctive differences between the expression profiles of PMF and ET. Notch, K-Ras, IL-8, and apoptosis pathways were altered the most in PMF as compared with controls. By contrast, cholesterol homeostasis, unfolded protein response, and hypoxia were the pathways found altered to the greatest degree in ET compared with control specimens. BM from PMF expressed a noncanonical transforming growth factor β (TGF-β) signature, which included activation of ID1, JUN, GADD45b, and genes with binding motifs for the JUN transcriptional complex AP1. By contrast, the expression of ID1 and GADD45b was not altered and there was a modest signal for JUN activation in ET. The similarities among PMF, liver fibrosis, and lung fibrosis were modest and included activation of integrin-α9 and tropomyosin-α1 between PMF and liver fibrosis, and of ectoderm-neural cortex protein 1 and FRAS1-related extracellular matrix protein 1 between PMF and lung fibrosis, but not TGF-β. These data identify TGF-β as a potential target for micro-environmental therapy in PMF.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Ishikawa G,Fujiwara N,Hirschfield H,Varricchio L,Hoshida Y,Barosi G,Rosti V,Padilla M,Mazzarini M,Friedman SL,Hoffman R,Migliaccio ARdoi
10.1016/j.exphem.2019.10.001subject
Has Abstractpub_date
2019-11-01 00:00:00pages
16-25.e3eissn
0301-472Xissn
1873-2399pii
S0301-472X(19)31072-0journal_volume
79pub_type
临床试验,杂志文章abstract:OBJECTIVE:Mesenchymal stem cells (MSCs) are capable of modulating the immune system through interaction with a wide range of immune cells. This study investigates the hypothesis that interaction of MSCs with macrophages could play a significant role in their antiinflammatory/immune modulatory effects. MATERIALS AND ME...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.09.004
更新日期:2009-12-01 00:00:00
abstract:OBJECTIVE:Diamond-Blackfan anemia (DBA) is a rare congenital hypoplastic anemia caused by mutations in ribosomal protein (RP) genes. Our aim is to develop gene therapy for DBA patients with mutations in RPS19. We previously demonstrated that RPS19 gene transfer partially corrects erythroid development in vitro. In this...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.06.012
更新日期:2008-11-01 00:00:00
abstract::G-banded metaphase chromosomes prepared from 14 male CBA/Ca mice with histologically confirmed myeloid leukemia (ML) were studied in an effort to identify specific chromosomal changes associated with radiation leukemogenesis. The chromosome studies were undertaken as part of a larger investigation of radiation carcino...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-03-01 00:00:00
abstract::T lymphocytes were derived by E-rosetting techniques from the peripheral blood and bone marrow of 12 healthy donors. Following incubation of 18 h with PWM, PHA, Con-A or culture medium (RPMI) alone, the lymphocytes were harvested by centrifugation and washed. Both lymphocytes and culture supernatants were tested for C...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1982-03-01 00:00:00
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:
更新日期:1985-05-01 00:00:00
abstract::Demineralized allogeneic bone matrix (DBM), implanted in muscle, induces the formation of an ossicle within which histologically recognizable hemopoietic tissue develops. Analyses of rabbit ossicle marrow in a methylcellulose culture system demonstrated the presence of committed hemopoietic precursors; colony-forming ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-07-01 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::Previous studies have suggested that in vivo granulocyte colony-stimulating factor (G-CSF) pharmacokinetics may change over time. We studied three patients treated with high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) for metastatic breast cancer after intravenous administration of reco...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1997-12-01 00:00:00
abstract::The effect of partially purified thrombopoietic stimulatory factor (TSF) on megakaryocytopoiesis was studied using the soft-gel colony-forming assay and a short-term marrow liquid culture system (STLC) and compared to the effects of megakaryocyte colony-stimulating activity present in pokeweed mitogen-stimulated splee...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-09-01 00:00:00
abstract::Fanconi anemia (FA) is a rare recessive disease characterized by progressive bone marrow failure, congenital abnormalities, and increased incidence of cancers. To date, mutations in 22 genes can cause FA or an FA-like phenotype. In China, in addition to clinical information, FA diagnosis primarily relies on genetic se...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2018.07.003
更新日期:2018-10-01 00:00:00
abstract::Addition of serum or plasma from many species increased the number and size of neutrophilic granulocyte and macrophage colonies formed in vitro by mouse bone marrow cells after stimulation by a variety of preparations containing colony stimulating factor (CSF). The active factor in serum was heat-labile, non-dialyzabl...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1975-08-01 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::Primary graft failure, secondary to either host-vs.-graft reaction or delayed engraftment, and graft-vs.-host disease (GVHD) are among the most difficult clinical problems to manage in the field of allogeneic bone marrow transplantation (BMT). Early diagnosis of both conditions would greatly improve their outcome. Usi...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:
更新日期:1998-05-01 00:00:00
abstract::Haemopoietic regeneration was studied following x-irradiation and transplantation of bone marrow from either normal or hydroxyurea-treated donor mice, to ascertain the contribution of proliferating progenitor cells to regeneration. With transplantation of equivalent numbers of CFU-S, total DNA and 3HTdR uptake into DN...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1977-09-01 00:00:00
abstract::Despite its growing use as a marker of proliferation, the relationship between expression of the nuclear antigen Ki67 and other indices of proliferation in acute myelogenous leukemia (AML) has not been elucidated. In this study, short-term primary suspension cultures of human AML bone marrow cells were used to compare...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-12-01 00:00:00
abstract::The rae28 gene (rae28) is a murine homologue of the Drosophila polyhomeotic gene, which is a member of the Polycomb-group genes. In this study, we examined the role of rae28 in lymphocyte development. Because homozygous rae28-deficient (rae28-/-) mice died in the perinatal period, we examined lymphocyte development by...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00620-2
更新日期:2001-01-01 00:00:00
abstract::Somatic mutations of calreticulin (CALR) have been observed in many cases of essential thrombocythemia (ET) or primary myelofibrosis that harbor non-mutated Janus kinase 2 (JAK2). CALR mainly localizes within the endoplasmic reticulum lumen, but a small fraction of the total CALR pool is distributed over the cell surf...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2016.05.001
更新日期:2016-09-01 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::We have investigated the effect of hematopoietic cytokines on the survival of severe combined immune-deficient (SCID) mice that received a high dose of radiation. In this study, female SCID mice were irradiated at doses ranging from 500 to 600 cGy and then transplanted with 2 x 10(6) male Balb/c marrow cells. Groups o...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1994-02-01 00:00:00
abstract::Mouse hematopoietic stem cells (HSCs) are highly enriched in the rare (approximately 0.05%) Thy-1.1(lo)Lin(-/lo)Sca-1+ fraction of hematopoietic tissues. It has been demonstrated that Thy-1.1(lo)Lin(-/lo)Sca-1+ cells are the only HSCs in C57BL/Ka-Thy-1.1 bone marrow. In this study, we separated C57/Ka-Thy-1.1 bone mar...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-04-01 00:00:00
abstract::In the human bone marrow the nuclear enzyme terminal deoxynucleotidyl transferase (TdT) is expressed by cells during early stages of lymphocyte differentiation. In order to investigate a possible regulation of lymphopoiesis at this level of differentiation, the relative frequency and the in vitro 3H-thymidine labeling...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract:OBJECTIVE:Osteoblasts play an important role in regulating hematopoiesis in the bone marrow. Here we show that U2-OS, a widely used osteoblastic cell line derived from an osteosarcoma, has the capacity to support proliferation of human hematopoietic progenitor cells in vitro. In this study, U2-OS cells are characterize...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00127-2
更新日期:2000-04-01 00:00:00
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
更新日期:2004-08-01 00:00:00
abstract::More than 2million human erythroblasts extrude their nuclei every second in bone marrow under hypoxic conditions (<7% O2). Enucleation requires specific signal transduction pathways and the local assembly of contractile actomyosin rings. However, the energy source driving these events has not yet been identified. We e...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2019.02.004
更新日期:2019-04-01 00:00:00
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
更新日期:2006-12-01 00:00:00
abstract::An increase in triglyceride synthesis has been observed in cultures of human bone marrow fibroblasts after the cells reach confluence. The addition of hydrocortisone further enhances triglyceride synthesis. Conditioned medium from confluent cultures also stimulates adipogenesis, probably mediated by a factor released ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-03-01 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::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
更新日期:2019-03-01 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::Overexpression of immune-related genes is widely reported in myelodysplastic syndromes (MDSs), and chronic immune stimulation increases the risk for developing MDS. Aberrant innate immune activation, such as that caused by increased toll-like receptor (TLR) signaling, in MDS can contribute to systemic effects on hemat...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2015.05.016
更新日期:2015-08-01 00:00:00