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 encouraging, emergence of primary and secondary resistance does occur in the majority of patients. Thus, it will be crucial to carefully characterize the activity of every single compound against different activating and resistance FLT3-internal tandem duplication (ITD) mutations. Here we tested the efficacy of sunitinib and sorafenib to inhibit primary FLT3 activating mutations (ITD and D835Y) and of secondary resistance mutations. METHODS:Ba/F3 cell lines stably expressing oncogenic FLT3 mutations were used to calculate cellular IC(50) values for sunitinib and sorafenib using cell proliferation assays. Differential IC(50) values for sorafenib toward FLT3-ITD and FLT3-D835Y were confirmed by Western blotting. Cell death was measured by propidium-iodide staining and flow cytometry. RESULTS:Sorafenib inhibits FLT3-ITD more potent than FLT3-D835Y, while sunitinib is equally effective against both mutant forms of FLT3. Importantly, sensitivity toward sorafenib and sunitinib varies between the different secondary FLT3-ITD resistance mutations. CONCLUSIONS:These results establish sensitivity profiles for the FLT3 inhibitors sunitinib and sorafenib. This may help to develop rational treatment strategies for acute myeloid leukemia with these compounds.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Kancha RK,Grundler R,Peschel C,Duyster Jdoi
10.1016/j.exphem.2007.07.008subject
Has Abstractpub_date
2007-10-01 00:00:00pages
1522-6issue
10eissn
0301-472Xissn
1873-2399pii
S0301-472X(07)00430-4journal_volume
35pub_type
杂志文章abstract::Using an accurate technique for staining and scoring soft agar cultures, this study defines the incidence of circulating CFUEOS in normal donors. With whole mononuclear cells as the source of colony stimulating factor (CSF) and fetal calf serum, 49.6% +/- 3.5 of the colonies were eosinophilic; with human placental con...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1982-03-01 00:00:00
abstract:OBJECTIVE:Adult T-cell leukemia (ATL) is a mature CD4(+) T-cell malignancy caused by infection with human T-lymphotrophic virus type-1 and is associated with a marked hypercalcemia in many patients. Recently, it has been proposed that macrophage inflammatory protein-1alpha (MIP-1alpha) is the clinical hallmark of hyper...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.11.013
更新日期:2008-04-01 00:00:00
abstract::In vitro colony formation by erythroid progenitors from the bone marrow was studied in 42 patients with a myelodysplastic syndrome using both a standard assay for growing erythroid colonies and an assay designed for growing megakaryocyte colonies. In the standard assay 5 patients had normal numbers of erythroid burst-...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-11-01 00:00:00
abstract:OBJECTIVE:Endothelial progenitor cells (EPCs) are used for angiogenic therapies or as biomarkers to assess cardiovascular disease risk. However, there is no uniform definition of an EPC, which confounds EPC studies. EPCs are widely described as cells that coexpress the cell-surface antigens CD34, AC133, and vascular en...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.04.002
更新日期:2007-07-01 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::Cells of two transplantable leukemias of mice, one myeloid and one lymphoid, were labeled with 51Cr in order to follow their distribution in hemopoietic and parenchymatous organs and blood of syngeneic recipients. Distribution of myeloid leukemia cells was compared with that of regenerating bone marrow cells and norma...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-01-01 00:00:00
abstract::The present studies evaluated effects of recombinant human (rhu) and murine (rmu) flt3 ligand (flt3-L) on colony formation by subsets of myeloid stem and progenitor cells present in low-density (LD) and cell-sorted CD34 hu cord blood (CB) and bone marrow (BM) cells and unseparated mu BM cells. By itself, flt3-L had we...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-09-01 00:00:00
abstract::We present the first report of a T-helper cell line, HUT 102, constitutively producing both granulocyte-macrophage colony-stimulating factor (GM-CSF) and monocytic colony-stimulating factor (M-CSF), as detected by sensitive enzyme-linked immunosorbent assays and Northern blot analysis. However, neither amplification n...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-11-01 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::Different human hematopoietic cell lines were analyzed for the presence of interleukin 6 (IL-6) and IL-6 receptor (IL-6-R). Both IL-6 mRNA and secreted active IL-6 protein were detectable in untreated cell lines with erythroid or megakaryoblastic features (K562, HEL, KU 812, MEG-01, and Dami), but they were not expres...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract:OBJECTIVE:To test gibbon ape leukemia virus (GALV) pseudotype vector transduction of marrow subpopulations that contribute to hematopoietic reconstitution in vivo. MATERIALS AND METHODS:Autologous CD34(+) Lin(-), CD34(+) Lin(+), and CD34(-) Lin(-) marrow cells, transduced by coculture with PG13/LN, PG13/LNX, and PG13/...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00137-5
更新日期:2000-05-01 00:00:00
abstract::Immunoenzymatic (IE) staining for antigen detection on intact human bone marrow (BM) colonies grown in agar layers is described. The reliability of this method allowed a study of antigenic changes during myelomonocytic differentiation. Phenotypic analysis was carried out at different times using the following monoclon...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-06-01 00:00:00
abstract::The survival rate and recovery of peripheral blood cells and platelets were studied in Balb/c mice subjected to different single doses of whole-body irradiation and treated with a combination of interleukin-3 (IL-3) and interleukin-11 (IL-11). In a first group of 20 mice, 7.5 Gy irradiation, immediately followed by 2 ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract:OBJECTIVE:Our previous study has shown that granulocyte-macrophage colony-stimulating factor (GM-CSF) gene/silica nanoparticles have a leukocytosis effect in normal dogs. Therefore, this study was conducted to determine whether treatment of canine GM-CSF gene/silica nanoparticles has preventive or therapeutic effects i...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.04.002
更新日期:2008-09-01 00:00:00
abstract:OBJECTIVE:Several transcription factors determine the cell fate decision between granulocytes and monocytes, but the upstream signal transduction pathways that govern myelopoiesis are largely unknown. Based on our observation of aberrant myeloid cell representation in hematopoietic tissues of 12/15-lipoxygenase (12/15-...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.07.004
更新日期:2010-11-01 00:00:00
abstract::Induced pluripotent stem cells (iPS) derived from disease cells are expected to provide a new experimental material, especially for diseases from which samples are difficult to obtain. In this study, we generated iPS from samples from patients with primary and secondary myelofibrosis. The primary myelofibrosis cells h...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2014.03.010
更新日期:2014-09-01 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::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: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:Our previous studies have demonstrated differentially expressed genetic signature patterns in adult peripheral blood (APB) monocytes (Mos) vs cord blood (CB) Mos. MATERIALS AND METHODS:In this study, we examined the differential gene expression profiles of APB vs CB immature dendritic cells (iDCs) and mature...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.07.010
更新日期:2009-10-01 00:00:00
abstract:BACKGROUND:Autologous bone marrow transplantation is an important therapy for patients with acute myelogenous leukemia (AML). However, leukemia in the graft may contribute to posttransplant relapse. Treatment of the graft with 4-hydroperoxycyclophosphamide (4HC) is sometimes used to decrease numbers of infused leukemia...
journal_title:Experimental hematology
pub_type: 杂志文章,多中心研究
doi:10.1016/s0301-472x(01)00732-9
更新日期:2001-11-01 00:00:00
abstract::The immediate hematopoietic response to 3'-azido-3'-deoxythymidine (AZT) was characterized in an unperturbed and regenerating mouse marrow model to identify the in vivo hematopoietic targets of AZT and test whether AZT toxicity is dependent on the proliferative activity of the hematopoietic targets. B6D2F1 mice receiv...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::Erythropoietin (Epo), a glycoprotein hormone, regulates the proliferation and differentiation of committed erythroid progenitor cells. We investigated the effect of Epo on the kinetics of an Epo-dependent cell line (DA-1ER), which was cloned from the murine interleukin 3-dependent cell line, DA-1. Flow cytometry and [...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-03-01 00:00:00
abstract:OBJECTIVE:Assays that can evaluate the potential of individual human hematopoietic stem cells (HSC) are still lacking. We previously developed the myeloid-lymphoid initiating cell (ML-IC) assay that enumerates single CD34(+) cells that generate long-term culture-initiating (LTC-IC) and NK-initiating (NK-IC) daughter ce...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.10.016
更新日期:2005-02-01 00:00:00
abstract::This study evaluated the usefulness of a matrix culture system, the artificial capillary culture system, for the growth of hematopoietic cells, the maintenance of CFUS and the collection of GM-CSF. The system was compared to monolayer, gelfoam sponge and Dexter liquid cultures. Monolayer cultures of adherent lymphohem...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1981-02-01 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:OBJECTIVE:Our laboratory reported that the angiotensin converting enzyme inhibitor captopril improves erythroid recovery from total body irradiation (TBI) in mice when administered after irradiation. However, captopril administered before TBI attenuates erythroid recovery. Here we investigate captopril and radiation re...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.12.002
更新日期:2011-03-01 00:00:00
abstract:OBJECTIVES:Processing of epigenomic transcriptional information by cell cycle phase G(1) and decision-making at checkpoint G(1)/S are the final organizational steps preceding gene replication in transcriptional reorientation programs (i.e., switches from proliferation to cycle arrest and neoplastic transformation). Fur...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2008.07.009
更新日期:2008-11-01 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::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