Abstract:
:In different types of myeloid leukemia, increased formation of reactive oxygen species (ROS) has been noted and associated with aspects of cell transformation, including the promotion of leukemic cell proliferation and migration, as well as DNA damage and accumulation of mutations. Work reviewed in this article has revealed the involvement of NADPH oxidase (NOX)-derived ROS downstream of oncogenic protein-tyrosine kinases in both processes, and the related pathways have been partially identified. FMS-like tyrosine kinase 3 with internal tandem duplications (FLT3-ITD), an important oncoprotein in a subset of acute myeloid leukemias, causes activation of AKT and, subsequently, stabilization of p22phox, a regulatory subunit for NOX1-4. This process is linked to ROS formation and DNA damage. Moreover, FLT3-ITD signaling through STAT5 enhances expression of NOX4, ROS formation, and inactivation of the protein-tyrosine phosphatase DEP-1/PTPRJ, a negative regulator of FLT3 signaling, by reversible oxidation of its catalytic cysteine residue. Genetic inactivation of NOX4 restores DEP-1 activity and attenuates cell transformation by FLT3-ITD in vitro and in vivo. Future work is required to further explore these mechanisms and their causal involvement in leukemic cell transformation, which may result in the identification of novel candidate targets for therapy.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Jayavelu AK,Moloney JN,Böhmer FD,Cotter TGdoi
10.1016/j.exphem.2016.08.008subject
Has Abstractpub_date
2016-12-01 00:00:00pages
1113-1122issue
12eissn
0301-472Xissn
1873-2399pii
S0301-472X(16)30570-7journal_volume
44pub_type
杂志文章,评审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::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 ident...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2017.08.003
更新日期:2017-11-01 00:00:00
abstract::Collagen gel was used as a substance for the assay of human granulocyte-macrophage colony-forming units (CFUc). The number of colonies formed in collagen gel was consistently higher than that in a conventional soft-agar system. In six out of eight experiments, the difference was statistically significant. Whole perman...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1984-05-01 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
abstract::Among 75 consecutive allogeneic bone marrow transplant recipients, 24 developed chronic graft-versus-host disease (GVHD), which was diagnosed from day 31 to day 368 after transplantation. Eight (33%) patients had more extensive chronic GVHD, and five patients died. The actuarial incidence of chronic GVHD was 48% at 40...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-11-01 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::A method for growing erythroid bursts from rat bone marrow cells is presented. The methylcellulose culture technique with rat spleen-conditioned medium was used. Successful growth of rat BFU-E was obtained with 20% fetal bovine serum when anemic rat plasma was used as the source of erythropoietin. Plating efficiency w...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-10-01 00:00:00
abstract:OBJECTIVE:The tumor suppressor p15Ink4b (Ink4b) is a cell-cycle inhibitor that is inactivated in a high percentage of acute myeloid leukemia and myeloid dysplasia syndrome cases. Despite this, the role of Ink4b in hematopoiesis remains unclear. Here we examined the role of Ink4b in blood cell formation using Ink4b-defi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.11.005
更新日期:2007-03-01 00:00:00
abstract::We previously demonstrated that lysis of tumor cells that express Hsp70, the highly stress-inducible member of the HSP70 family, on their plasma membrane is mediated by natural killer (NK) cells. Here, we studied the effects of different proteins of the HSP70 family in combination with interleukin 2 (IL-2) on the prol...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(99)00104-6
更新日期:1999-11-01 00:00:00
abstract::Hematopoietic stem cells (HSC) rely on a highly regulated molecular network to balance self-renewal and lineage specification to sustain life-long hematopoiesis. Despite a plethora of studies aimed at identifying molecules governing HSC fate, our current knowledge of the genes responsible is limited. We have found ins...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2016.01.010
更新日期:2016-05-01 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::A right atrial catheter was implanted into 15 patients undergoing bone marrow transplantation as a treatment for acute leukemia. The catheter remained in position for 79 +/- 34 days. No catheter-related septicemia was observed. It appears that this catheter is helpful in supporting bone marrow transplant recipients. ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-08-01 00:00:00
abstract::Recently we have described a CD4+ human T-cell hybridoma Ft.F3 (ATCC HB 9713). This hybridoma produces two proteins having molecular weights of 29 kd (P29) and 14.7 kd (P14.7) that function as activators of human monocyte tumor cytotoxicity and interleukin 1 (IL-1) synthesis (macrophage cytotoxicity-inducing factors, ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-08-01 00:00:00
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...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2018.12.007
更新日期:2019-04-01 00:00:00
abstract::Dtk (Tyro 3/Sky/Rse/Brt/Tif) belongs to a recently recognized subfamily of receptor tyrosine kinases that also includes Ufo (Axl/Ark) and Mer (Eyk). Ligands for Dtk and Ufo have been identified as protein S and the related molecule Gas6, respectively. This study examined expression of Dtk during ontogeny of the hemato...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::An in vitro culture technique for colony formation of marrow cells and peripheral blood cells from untreated acute leukemia patients and from patients in relapse is described. The colonies from bone marrow cells of an untreated acute myelogenous leukemia (AML) patient were demonstrated to be of leukemic origin by cyto...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1983-04-01 00:00:00
abstract:OBJECTIVE:The ABCG2 transporter has been identified as a determinant of the side population (SP) in murine bone marrow and a potential marker for primitive stem cells. To assess the potential of the SP phenotype and ABCG2 expression to identify stem cells in human umbilical cord blood (hUCB), we have examined directly ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.09.015
更新日期:2009-02-01 00:00:00
abstract::In this report, the effects of adenosine on the promyelocytic cell line HL-60 and on T-lymphocytic clones are compared. According to previous reports, adenosine induces a dose-dependent inhibition of DNA synthesis in T-lymphocytes. Conversely, adenosine dose-dependently enhances DNA synthesis in HL-60 cells, as docume...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-11-01 00:00:00
abstract::Mouse megakaryocyte colonies developed in a fibrin clot culture system were morphologically classified into three types: immature homogeneous (IH), heterogeneous (H), and mature homogeneous (MH) colonies. The colony size (number of megakaryocytes per colony), the ploidy distribution of megakaryocytes in colonies, and ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-06-01 00:00:00
abstract::Induced pluripotent stem cells (iPSCs) can be generated from various types of cells with transduction of defined transcription factors. Patient-derived iPSCs are becoming commonly utilized for understanding the molecular pathways involved in disease and for the development of novel targeted therapies. With the use of ...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2015.06.006
更新日期:2015-08-01 00:00:00
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:
更新日期:1994-12-01 00:00:00
abstract::Antisera from rabbits immunized with murine macrophage colony-stimulating factor (CSF-1) were evaluated for cross-reactivity with human urine CSF-1. One cross-reactive antiserum was used to purify CSF from human urine. The IgG fractions from normal rabbit serum and the anti-CSF serum were bound to cyanogen bromide-act...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to develop novel markers for enrichment of hematopoietic progenitors from bone marrow of swine. MATERIALS AND METHODS:We previously showed that pig bone marrow contains a "side population" (SP) of Hoechst dye-effluxing cells that resembles the hematopoietic stem cell (HSC)-containin...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00835-4
更新日期:2002-07-01 00:00:00
abstract::Assessment of donor chimerism is becoming increasingly important in patients undergoing reduced-intensity conditioning (RIC) allogeneic bone marrow transplants, due to the possibility of mixed chimeras. This regimen has been used successfully for patients with leukemia and genetic disorders with donor chimerism occurr...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.05.028
更新日期:2004-09-01 00:00:00
abstract::Cell proliferation was investigated in normal and Rauscher Leukemia Virus-infected BALB/c mice. Five days after inoculation, islands of leukemic blasts arose in the red pulp, and proliferated as shown by autoradiographic analysis after a pulse of 3H-Thymidine. These cells subsequently infiltrated the whole spleen and ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-06-01 00:00:00
abstract::Disruption of ribosomal proteins is associated with hematopoietic phenotypes in cell culture and animal models. Mutations in ribosomal proteins are seen in patients with Diamond Blackfan anemia, a rare congenital disease characterized by red cell aplasia and distinctive craniofacial anomalies. A zebrafish screen uncov...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2011.11.007
更新日期:2012-03-01 00:00:00
abstract::The processing of inflammatory signals occurs through a variety of mechanisms; the recent descriptions of the tethered ligand receptor for thrombin (JA Hoxie et al., J Biol Chem 268:13756, and TK Vu et al., Cell 64:1057) provide a novel route and mechanism for cellular activation after inflammation and thrombosis. Usi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-07-01 00:00:00
abstract::Functional recovery of the immune system is critical for long-term survival in hematopoietic stem cell transplant recipients. In this study, two donor-recipient allogeneic transplant settings (haploidentical and fully mismatched) are used to investigate the functional activity of donor-derived B and T cells in animals...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00554-3
更新日期:2000-12-01 00:00:00
abstract::Committed erythroid progenitor cells (Colony Forming Units-Erythroid, CFU-E) have been studied in canine cyclic hematopoiesis (CH) utilizing a semi-solid methyl cellulose culture system. Erythroid colonies were stimulated by the addition of a standard volume of serum from normal dogs that had been phlebotomized and su...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-10-01 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