Abstract：
:The myeloproliferative neoplasms (MPNs) are somatic mutation-driven hematologic malignancies characterized by bone marrow fibrosis and the accumulation of atypical megakaryocytes with reduced polyploidization in the primary myelofibrosis subtype of the MPNs. Increasing evidence points to a dominant role of abnormal megakaryocytes in disease initiation and progression. Here we review the literature related to kinase signaling pathways relevant to megakaryocyte differentiation and proliferation, including Aurora A kinase, RhoA/ROCK, and JAK/STAT, as well as the activities of their targeted inhibitors in models of the disease. Some of these pathway inhibitors selectively induce megakaryocyte differentiation, suppress malignant proliferation, and promote polyploidization and proplatelet formation. Moreover, combining sets of these inhibitors may be an effective approach to treat and potentially cure MPN patients. For example, preclinical studies reported significant synergistic effects of the combination of an Aurora A inhibitor and JAK1/2 inhibitor, in a murine model of the primary myelofibrosis. Future basic and clinical research into the contributions of these signaling pathways to aberrant megakaryopoiesis may lead to novel effective treatments for MPN patients.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Yang Q,Crispino JD,Wen QJdoi
10.1016/j.exphem.2016.12.007subject
Has Abstractpub_date
2017-04-01 00:00:00pages
32-38eissn
0301-472Xissn
1873-2399pii
S0301-472X(16)30775-5journal_volume
48pub_type
杂志文章,评审abstract：:The fate of hematopoietic progenitor cells (HPCs) in the bone marrow (BM) microenvironment is determined by two different interactions: 1) they adhere (via integrins) to both extracellular matrix molecules and BM stromal cells; and 2) stromal cells produce cytokines that influence their survival, proliferation, differ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1998-08-01 00:00:00
abstract：:The selection of chemotherapy regimen for elderly patients with acute myeloid leukemia (AML) remains challenging. Here, we report that granulocyte colony-stimulating factor (G-CSF) upregulates the expression of microRNA (miR)-146a in a nuclear factor kappaB-dependent manner, leading to direct decreases in the expressi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2018.09.002
更新日期：2018-12-01 00:00:00
abstract：:Infusion of large numbers of donor regulatory T cells (Tregs) is an effective approach to suppress graft-versus-host disease (GvHD). We have reported previously that enhancing the killing activity of CD25(+) Tregs by decoration with short-lived Fas-ligand (FasL) protein (killer Tregs) is effective in abrogation of aut...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2013.04.016
更新日期：2013-10-01 00:00:00
abstract：OBJECTIVE:Several transducing molecules, including JAK2, STAT5, MAP kinases, phosphatidylinositol 3-kinase (PI3K), phospholipase C-gamma1, and PKC are activated by interaction between erythropoietin (EPO) and the EPO receptor. The aim of this was to examine the relative involvement of PI3K in the development of glycoph...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00868-8
更新日期：2002-09-01 00:00:00
abstract：:Bone marrow endothelial cells are likely to play an important role in the homing of hematopoietic progenitor cells. In view of analyzing the interactions between endothelial cells and hematopoietic progenitor cells, we studied several methods of isolating endothelial cells from human bone marrow, including fluorescenc...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-01-01 00:00:00
abstract：:Current next-generation sequencing (NGS) technologies allow unprecedented insights into the mutational profiles of tumors. Recent studies in myeloproliferative neoplasms have further demonstrated that, not only the mutational profile, but also the order in which these mutations are acquired is relevant for our underst...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2017.09.011
更新日期：2018-01-01 00:00:00
abstract：:A fluorescence-activated cell sorter has been used to sort out enriched populations of murine hemopoietic stem cells from mouse bone marrow, based on fluorescence of cells labeled with various antisera. Significant positive enrichment for stem cells was obtained with rabbit anti-human brain, human anti-human sperm and...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1979-08-01 00:00:00
abstract：:Anemia is a frequently observed adverse effect in cancer patients who receive chemotherapy or drugs designed to block specific oncogenic signaling pathways, although the underlying mechanisms are poorly understood. An article first published online (Zhu HH, Luo X, Zhang K, et al. Proc Natl Acad Sci USA 2015;112:13342-...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2016.01.004
更新日期：2016-05-01 00:00:00
abstract：:It is a well recognized problem that sample derived transferrin-bound iron (Tf-Fe) interferes with radio-iron incorporation into heme in the in vitro assay of erythropoietin (Ep) using fetal mouse liver cells (FMLC). This paper describes a mathematical procedure to correct for the unknown quantity of "cold" Tf-Fe in a...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1981-08-01 00:00:00
abstract：:Fourteen patients with chronic granulocytic leukemia received bone marrow grafts from HLA identical siblings. Ten patients were in blast crisis prior to grafting, three were in an accelerated phase of their disease, and one was aplastic secondary to chemotherapy. Prior to transplant all patients were conditioned with ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1978-10-01 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：: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：
更新日期：1980-09-01 00:00:00
abstract：:Multiple myeloma (MM) is a hematologic malignancy characterized as an abnormal proliferation and invasion of plasma cells into the bone marrow. Toll-like receptors (ТLRs) connect the innate and adaptive immune responses and represent a significant and potentially linking element between inflammation and cancer. When T...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2014.11.003
更新日期：2015-03-01 00:00:00
abstract：OBJECTIVE:Myeloid ectropic viral integration site 1 (MEIS1) is a Hox cofactor known for its role in development and is strongly linked to normal and leukemic hematopoiesis. Although previous studies have focused on identifying protein partners of MEIS1 and its transcriptionally regulated targets, little is known about ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2010.06.006
更新日期：2010-09-01 00:00:00
abstract：OBJECTIVE:Clonal stem cell proliferation and increased erythrocyte mass are hallmarks of the myeloproliferative disorder polycythemia vera (PV). The molecular basis of PV is unknown. METHODS:We carried out a genome-wide screening for loss of heterozygosity (LOH) and analyzed candidate genes within the LOH loci. RESUL...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(01)00789-5
更新日期：2002-03-01 00:00:00
abstract：OBJECTIVE:We previously showed enhanced engraftment of human T cells in the transgenic NonObese Diabetic/severe combined immunodeficient (NOD/scid)-DR1 mice, compared to NOD/scid mice. We now characterize their immunobiology, innate immunity, and intrahepatic neonatal engraftment of cord blood mononuclear cells (CBMNC)...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.05.002
更新日期：2007-08-01 00:00:00
abstract：:Transfusion with 10,000 or 20,000 marrow cells resulted in 30+ days survival of 15%-50% of mice exposed to an Ld90 or LD100 or radiation. The use of congenic mice with alloenzyme markers permitted the identification of host and donor cells in the peripheral blood of transfused animals. Donor cells were present initial...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-08-01 00:00:00
abstract：:Bone marrow cell responses to therapeutic doses of cis-diamminedichloroplatinum (II) (Cis-Pt) were evaluated in female C57B1/6 mice by determining bone marrow cellularity and content of transplantable colony forming units (CFUS) after treatment. Although limitation on the dosage of Cis-Pt is generally considered to be...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1981-03-01 00:00:00
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
更新日期：2003-10-01 00:00:00
abstract：:Acute disseminated intravascular coagulation (DIC) is a life-threatening condition that may be encountered in many situations, especially in cases of shock with uncontrollable hemorrhage. Anisodamine, an alkaloid extracted from a Chinese herb, is well known for its dramatic therapeutic effect on DIC. Sixty male rabbit...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1987-01-01 00:00:00
abstract：:Rats made transiently neutropenic by intra-arterial administration of vinblastine (3 mg/kg) and infected with E. coli (6.02+/-0.45 X 10(8), per animal) have a mortality rate of 90% within 48 h post infection. Multiple transfusions of large numbers of granulocytes (harvested from Deca-Durabolin treated donor rats) prot...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1977-05-01 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：OBJECTIVE:We previously demonstrated that CD8(+)/TCR(-) bone marrow cells facilitate engraftment of HSC in allogeneic recipients without causing graft-vs-host disease. Whether facilitating cells (FC) develop from T cells or represent a distinct lineage has not been determined. METHODS:In the present studies, we charac...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2004.07.011
更新日期：2004-10-01 00:00:00
abstract：:We previously reported an in vitro bioassay permissive to eosinophil production from naive mouse bone marrow cells. Based on cytosmear analysis, recombinant murine (rm) interleukin (IL)-3 combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) provided better quantitative cellular yields compared with ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1998-06-01 00:00:00
abstract：:When cultured mast cells of (WB X C57BL/6)F1-+/+(WBB6F1-+/+) and WB-+/+(WB) mice were directly injected into the skin of genetically mast cell-deficient WBB6F1-W/Wv mice, mast cell clusters appeared at the injection sites. Although in vitro colony-forming ability is comparable between cultured mast cells of WB mice an...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-12-01 00:00:00
abstract：:This study is about enrichment of hemopoietic stem cell concentration in mouse bone marrow by use of a glass wool filtration technique. Maximum stem cell concentration was accomplished when filtration conditions were as follows: (1) support medium supplemented to 15% with fresh serum from syngeneic donors; (2) no incu...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1977-01-01 00:00:00
abstract：OBJECTIVE:Activated platelets participate in inflammatory and microbicidal processes by upregulation of surface selectins, shedding of CD40 ligand, and release of platelet microbicidal proteins and microparticles. Given their myeloid lineage, we hypothesized that platelets express functional N-formyl peptide receptors ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2004.09.010
更新日期：2005-01-01 00:00:00
abstract：:The course of development of graft-versus-host reactions (GVHR) following lethal irradiation was compared in two mouse donor-host combinations disparate at non H-2 loci alone or associated to H-2 complex. The pathogenesis of these reactions was very different (mortality rates faster in the second situation for example...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1981-05-01 00:00:00
abstract：OBJECTIVE:TGF-beta1 is a powerful inhibitor of erythropoiesis. However, its mechanisms of action are not fully elucidated yet at the cellular level. In this work we have studied the effects of TGF-beta on UT-7 cell survival, proliferation and differentiation. MATERIALS AND METHODS:UT-7 cell line is strictly dependent ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(99)00155-1
更新日期：2000-03-01 00:00:00
abstract：:The extent of incorporation of bromodeoxyuridine (BrdUrd) into DNA of different types of hematopoietic stem cells assayed in vivo and of progenitor cells assayed in vitro was determined after continuous infusion of BrdUrd into mice for either four or seven days. Cells surviving subsequent exposure to 320 nm ultraviole...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1984-10-01 00:00:00
