Abstract：
:Acute myeloid leukemia (AML) is a disease with a poor prognosis. It has been demonstrated that AML cells express vascular endothelial growth factor (VEGF) as well as Flt-1 and KDR, resulting in an autocrine pathway for cell survival. PTK787/ZK 222584 is a new oral antiangiogenic molecule that inhibits tyrosine kinase activity of all known VEGF receptors. The present study aimed to investigate the therapeutic efficacy of combining PTK787/ZK 222584 with a chemotherapeutic agent, such as Idarubicin, for treatment of AML. We have analyzed in four AML cell lines and seven AML patient samples, cell proliferation, apoptosis, angiogenesis. and activation of several related intracellular pathways after treatment with PTK787/ZK 222584 alone or combined with Idarubicin. PTK787/ZK 222584 decreased VEGF levels and VEGF receptor phosphorylation in the AML cells showing Fms-like tyrosine kinase 3/internal tandem duplication mutation (Flt3/ITD). Both drugs, given separately, inhibited cell proliferation and promoted apoptosis. Moreover, combined treatment promoted more apoptosis and inhibition of cell proliferation than each compound administered separately in all AML cells. In conclusion, PTK787/ZK 222584 combined with Idarubicin achieved a better therapeutic efficacy than chemotherapy alone in AML cells, especially in those with Flt3/ITD, in which the combination further prevented activation of the angiogenic process.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Barbarroja N,Torres LA,Luque MJ,Carretero RM,Valverde-Estepa A,Lopez-Sanchez LM,Rodriguez-Ariza A,Velasco F,Torres A,López-Pedrera Cdoi
10.1016/j.exphem.2009.03.001subject
Has Abstractpub_date
2009-06-01 00:00:00pages
679-91issue
6eissn
0301-472Xissn
1873-2399pii
S0301-472X(09)00079-4journal_volume
37pub_type
杂志文章abstract：:We studied the phenotypic and functional properties of colony-forming cells (CFCs), primitive long-term culture initiating cells (LTC-ICs) and lymphoid precursors present in human fetal liver (FL) and compared these with their adult bone marrow (BM) counterparts. FL (7-14-week) cells were selected by fluorescence-acti...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1997-05-01 00:00:00
abstract：:Remarkable advances have been made in bone marrow transplantation (BMT), which now has become a powerful strategy for the treatment of leukemia, aplastic anemia, congenital immunodeficiency disorders, and autoimmune diseases. Using various animal models, allogeneic BMT has been found to be useful in the treatment of a...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/s0301-472x(01)00645-2
更新日期：2001-06-01 00:00:00
abstract：:Patients who undergo autologous bone marrow transplantation for acute leukemia are at high risk for relapse. We have evaluated the feasibility of administering cell-mediated immunotherapy with family-related haploidentical lymphocytes following autologous bone marrow transplantation in order to evoke a graft-vs-leukem...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(00)00533-6
更新日期：2000-11-01 00:00:00
abstract：OBJECTIVE:The CD15 (Lewis x) cell surface oligosaccharide moiety is expressed in a variety of normal and tumor cells and recognized by selectins. The detection of CD15 on malignant Hodgkin-Reed-Sternberg (HRS) cells serves as a diagnostic marker of Hodgkin's lymphoma (HL). Retrospective studies suggest that the express...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(03)00237-6
更新日期：2003-11-01 00:00:00
abstract：OBJECTIVE:We studied two adult brothers with severe congenital thrombocytopenia in order to determine the genetic etiology of their inherited disorder. Despite the absence of eczema or immunodeficiency, a mutation of the Wiskott-Aldrich syndrome (WAS) gene was suspected because of the presence of microthrombocytes. MA...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)01023-8
更新日期：2003-02-01 00:00:00
abstract：:In the accompanying paper we constructed a model for the proliferation and differentiation of granulocyte-macrophage progenitor cells in response to the specific proliferation/differentiation stimulus granulocyte-macrophage colony-stimulating activity (gm-CSA). Here we have tested the model without altering the model ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1985-02-01 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：:Peripheral blood lymphocytes obtained at 24-30 months after birth from a male with X-linked severe combined immune deficiency maintained in a gnotobiotic environment were characterized by T and B cell surface markers. A high proportion (55-80 percent) of circulating lymphocytes bore surface IgM as detected by direct i...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1976-01-01 00:00:00
abstract：:Previous studies in animal models have suggested that bone marrow-derived interleukin-2 (IL-2) activated natural killer (A-NK*) cells can be used to eliminate residual leukemic cells both in vivo and in vitro. As part of initial studies to develop a clinical protocol to exploit this phenomenon in combination with cult...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-08-01 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：OBJECTIVE:The purpose of this study was to investigate the effects of interleukin-2 (IL-2) gene-transduced hematopoietic progenitor cells or cytotoxic function and systemic toxicity following syngeneic bone marrow transplantation. MATERIAL AND METHODS:Marrow of 5-fluorouracil pretreated donor mice were transfected wit...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(00)00487-2
更新日期：2000-08-01 00:00:00
abstract：:Stem cell maintenance in continuous bone marrow culture has been shown to be associated with close range interaction between hematopoietic cells and marrow derived adherent cells (MDAC). The extent to which the culture system is dependent upon this type of interaction has not been ascertained. Explants of non-adherent...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1981-03-01 00:00:00
abstract：:We have recently shown that interleukin 6 (IL-6) induces transient expression of the alpha-chain of the interleukin 2 receptor (IL-2R alpha) in the murine leukemia myeloid M1 cell line. Others have reported that IL-6 and interleukin 1 (IL-1) synergistically enhance the expression of IL-2R alpha in T cells. Thus, in th...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1992-11-01 00:00:00
abstract：:With a new labeling technique in radiation chimeras, an attempt was made to determine the duration of the phases of the stem cell cycle including shortest and mean generation time and to estimate the number of hemopoietic stem cells per unit of bone marrow cellularity. The DNA of bone marrow cells in DNA synthesis was...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1979-10-01 00:00:00
abstract：:The cloning efficiency of T-lymphocyte progenitor cells (CFU-T) is dependent on mononuclear cell concentration, with a triphasic growth curve. At low plating cell concentrations, hydrocortisone causes a dose-dependent decrease in cloning efficiency, whereas at high cell concentrations hydrocortisone causes increased c...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-02-01 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：:As a result of the introduction of new sequencing technologies, the molecular landscape of acute myeloid leukemia (AML) is rapidly evolving. From karyotyping, which detects only large genomic aberrations of metaphase chromosomes, we have moved into an era when sequencing of each base pair allows us to define the AML g...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2015.05.009
更新日期：2015-08-01 00:00:00
abstract：OBJECTIVE:The present study was designed to compare directly the frequency of circulating LTC-IC and E-LTC-IC mobilized in peripheral blood (PB) after chemotherapy supported by either G-CSF (PB-G) or GM-CSF (PB-GM) in comparison to steady-state bone marrow (BM) and PB (PB-ST) values in the same patients. MATERIALS AND...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(01)00762-7
更新日期：2002-01-01 00:00:00
abstract：:The tumor suppressor p53 is thought to play a role in megakaryocyte (MK) development. To assess the influence of the p53 regulatory pathway further, we studied the effect of RG7112, a small molecule MDM2 antagonist that activates p53 by preventing its interaction with MDM2, on normal megakaryocytopoiesis and platelet ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2013.11.012
更新日期：2014-02-01 00:00:00
abstract：OBJECTIVE:Donor lymphocyte transfusions (DLT) are effective in the treatment of leukemia after allogeneic stem cell transplantation. Graft-vs-host-disease (GVHD) is the major risk factor of DLT. In dog leukocyte antigen (DLA)-identical littermate dogs, DLT given within 3 weeks after transplantation of marrow depleted o...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2009.05.001
更新日期：2009-08-01 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：:The influence of erythrocytes, extracts of erythrocytes and hemin was assessed on colony formation in vitro by human bone marrow multipotential (CFUGEMM), erythroid (BFUE) and granulocyte-macrophage (CFUGM) progenitor cells. Colony formation by CFUGEMM and BFUE present in the low density (less than 1.077 g/cm3) fracti...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1983-09-01 00:00:00
abstract：:A human acute myelomonocytic leukemia cell line, KBM-3, was developed to study the pathophysiology of human acute myeloid leukemia. This cell line was characterized by morphology, immunophenotype, Giemsa-banding pattern, in vitro proliferation capacity, and tumorigenicity in nude mice. The KBM-3 cell line was establis...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1992-03-01 00:00:00
abstract：:A homogeneous population of mast cells was obtained by culturing bone marrow cells of WBB6F1(-)+/+ mice. The proliferation of the cultured mast cells in diffusion chambers was investigated to examine whether the diffusion chamber technique was applicable for study of the regulation of mast cell proliferation. WBB6F1-W...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
abstract：:Fractionated whole body irradiation induces thymic lymphomas in C57 BL/Ka mice after 6-12 months. A graft of normal congenic bone marrow cells immediately after the last irradiation prevents the development of lymphomas by inducing the disappearance of preleukemic cells. When such a graft is performed one month later,...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1997-02-01 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：:The transcription factor SCL is critically required for establishing hematopoiesis and for proper endothelial development, but not for maintenance of hematopoietic stem cells or endothelial cells in the adult. Conflicting data exists regarding the developmental function of SCL, namely, whether it acts as a master regu...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.07.005
更新日期：2008-12-01 00:00:00
abstract：OBJECTIVE:CD34(+) cells, present within the bone marrow, have previously been shown to possess pancreatic endocrine potential. Based on this observation, we explored the capacity of CD34(+) cells derived in culture from the differentiation of human embryonic stem cells (hESC), for their in vivo pancreatic endocrine cap...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2010.03.002
更新日期：2010-06-01 00:00:00
abstract：:In chronic eosinophilic leukemia, the transforming oncoprotein FIP1L1-PDGFRA is a major target of therapy. In most patients, the tyrosine kinase inhibitor (TKI) imatinib induces complete remission. For patients who are intolerant or resistant, novel TKIs have been proposed. We examined the in vitro effects of 14 kinas...
journal_title：Experimental hematology
pub_type： 临床试验,杂志文章
doi：10.1016/j.exphem.2013.12.007
更新日期：2014-04-01 00:00:00
abstract：:The long-term effects of a maximum tolerated dose of doxorubicin (ADR) (10 mg/kg, LD10/60) on the recovery of the hematopoietic compartments of the femoral marrow from radiation (450 rad) were investigated over a 32-week interval using a mouse model. Comparative radiation response curves, estimating hematopoietic prol...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1985-01-01 00:00:00
