Search results for "fms-Like Tyrosine Kinase 3"

showing 10 items of 28 documents

NUOVI AGENTI TERAPEUTICI PER IL TRATTAMENTO DI PATOLOGIE EMATOLOGICHE

2019

La presente invenzione si riferisce al campo di nuove molecole tetracicliche, aventi un sistema tetraciclico, e loro impiego come medicamenti di patologie ematologiche in particolare per il trattamento della leucemia mieloide acuta (AML) in pazienti emizigoti FLT3/ITD resistenti alle terapie convenzionali.

2H-Imidazo [2'1':23][13]thiazolo[45-e]isoindol-8-yl)phenyl]ureas Acute myeloid leukemia (AML) Internal tandem duplication (ITD) FMS-like tyrosine kinase 3 (FLT3) FLT3/ITDSettore CHIM/08 - Chimica Farmaceutica
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NEW THERAPEUTIC AGENTS FOR THE TREATMENT OF HAEMATOLOGICAL PATHOLOGIES

2021

2H-Imidazo [2'1':23][13]thiazolo[45-e]isoindol-8-yl-phenylureas Acute myeloid leukemia (AML) Internal tandem duplication (ITD) FMS-like tyrosine kinase 3 (FLT3) FLT3/ITD
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Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled…

2019

Background Patients with relapsed or refractory FLT3 internal tandem duplication (FLT3-ITD)-positive acute myeloid leukaemia have a poor prognosis, including high frequency of relapse, poorer response to salvage therapy, and shorter overall survival than those with FLT3 wild-type disease. We aimed to assess whether single-agent quizartinib, an oral, highly potent and selective type II FLT3 inhibitor, improves overall survival versus salvage chemotherapy. Methods QuANTUM-R is a randomised, controlled, phase 3 trial done at 152 hospitals and cancer centres in 19 countries. Eligible patients aged 18 years or older with ECOG performance status 0-2 with relapsed or refractory (duration of first …

AdultMale0301 basic medicinemedicine.medical_specialtyPopulationSalvage therapy/Gastroenterology03 medical and health scienceschemistry.chemical_compound0302 clinical medicineInternal medicinemedicineHumansBenzothiazoleseducationSurvival rateAgedQuizartinibSalvage Therapyeducation.field_of_studybusiness.industryPhenylurea CompoundsMiddle Agedmedicine.diseaseFludarabineSurvival RateTransplantationLeukemia Myeloid AcuteSettore MED/15 - MALATTIE DEL SANGUE030104 developmental biologyfms-Like Tyrosine Kinase 3OncologychemistryTandem Repeat Sequences030220 oncology & carcinogenesisCytarabineFemaleNeoplasm Recurrence LocalbusinessFebrile neutropeniamedicine.drug
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The kinase inhibitor LS104 induces apoptosis, enhances cytotoxic effects of chemotherapeutic drugs and is targeting the receptor tyrosine kinase FLT3…

2008

Activating mutations of FLT3 are found in approximately one-third of acute myeloid leukemia (AML)-cases and are considered to represent an attractive therapeutic target. In this study, we report that the hydroxystyryl-acrylonitrile compound LS104 inhibits proliferation and induces potent cytotoxic effects in FLT3 expressing leukemic cells in vitro. Immunoblot and phosphoprotein-FACS analysis demonstrated inhibiton of phosphorylation of FLT3-ITD and of its downstream targets. In pharmacokinetic studies, a rapid and dose dependent cellular uptake of LS104 lasting up to 11h could be demonstrated. Combination of LS104 with chemotherapeutic agents markedly enhanced cytotoxic effects. Recently, a…

AdultMaleCancer ResearchDaunorubicinmedicine.drug_classBlotting WesternFluorescent Antibody TechniqueApoptosisPharmacologyReceptor tyrosine kinaseTyrosine-kinase inhibitorStyrenesColony-Forming Units AssayMiceBone Marrowhemic and lymphatic diseasesAntineoplastic Combined Chemotherapy ProtocolsmedicineTumor Cells CulturedCD135AnimalsHumansPoint MutationTissue DistributionAgedCell ProliferationAged 80 and overbiologyAcrylonitrileDaunorubicinCytarabineMyeloid leukemiaCell DifferentiationHematologyMiddle Agedmedicine.diseaseLeukemiaLeukemia Myeloid AcuteOncologyfms-Like Tyrosine Kinase 3Fms-Like Tyrosine Kinase 3Cytarabinebiology.proteinCancer researchDrug Therapy CombinationFemalemedicine.drugSignal TransductionLeukemia research
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miR-155 regulative network in FLT3 mutated acute myeloid leukemia

2015

Abstract Background Acute myeloid leukemia (AML) represents a heterogeneous disorder with recurrent chromosomal alterations and molecular abnormalities. Among AML with normal karyotype (NK-AML) FLT3 activating mutation, internal tandem duplication (FLT3-ITD), is present in about 30% of patients, conferring unfavorable outcome. Our previous data demonstrated specific up-regulation of miR-155 in FLT3-ITD+ AML. miR-155 is known to be directly implicated in normal hematopoiesis and in some pathologies such as myeloid hyperplasia and acute lymphoblastic leukemia. Methods and results To investigate about the potential influence of miR-155 de-regulation in FLT3-mutated AML we generated a transcrip…

AdultMaleCancer ResearchMyeloidJUNBNetworkBiologyYoung Adultchemistry.chemical_compoundAMLhemic and lymphatic diseasesmicroRNACEBPBmedicineHumansGene silencingGene Regulatory NetworksAML; MicroRNA; NetworkAgedAged 80 and overGene Expression Regulation LeukemicGene Expression ProfilingMyeloid leukemiaMicroRNAHematologyMiddle AgedLeukemia Myeloid AcuteMicroRNAsmedicine.anatomical_structurefms-Like Tyrosine Kinase 3OncologyRUNX1chemistryMutationCancer researchFemaleMyelopoiesisK562 Cells
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Differential expression of specific microRNA and their targets in acute myeloid leukemia

2010

Acute myeloid leukemia (AML) the most common acute leukemia in adults is characterized by various cytogenetic and molecular abnormalities. However, the genetic etiology of the disease is not yet fully understood. MicroRNAs (miRNA) are small noncoding RNAs which regulate the expression of target mRNAs both at transcriptional and translational level. In recent years, miRNAs have been identified as a novel mechanism in gene regulation, which show variable expression during myeloid differentiation. We studied miRNA expression of leukemic blasts of 29 cases of newly diagnosed and genetically defined AML using quantitative reverse transcription polymerase chain reaction (RT-PCR) for 365 human miR…

AdultMaleNPM1Down-RegulationBiologySettore MED/15 - Malattie Del SangueYoung Adulthemic and lymphatic diseasesmicroRNAmedicineGene silencingHumansLeukemia microarray data microRNAGranulocyte Precursor CellsAgedCell ProliferationGeneticsRegulation of gene expressionAged 80 and overAcute leukemiaReverse Transcriptase Polymerase Chain ReactionGene Expression ProfilingCore Binding FactorsMyeloid leukemiaNuclear ProteinsCell DifferentiationHematologyMiddle Agedmedicine.diseaseUp-RegulationGene expression profilingGene Expression Regulation NeoplasticLeukemiaLeukemia Myeloid AcuteMicroRNAsfms-Like Tyrosine Kinase 3Case-Control StudiesMutationFemaleSettore SECS-S/01 - StatisticaNucleophosmin
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Novel 3-Azaindolyl-4-arylmaleimides Exhibiting Potent Antiangiogenic Efficacy, Protein Kinase Inhibition, and Antiproliferative Activity

2012

Tumor growth and metastasis are highly associated with the overexpression of protein kinases (PKs) regulating cell growth, apoptosis resistance, and prolonged cell survival. This study describes novel azaindolyl-maleimides with significant inhibition of PKs, such as VEGFR, FLT-3, and GSK-3β which are related to carcinogenesis. Furthermore, these compounds exhibit high kinase selectivity and potent inhibition of angiogenesis and cell proliferation, offering versatile options in cancer treatment strategies.

AngiogenesisAngiogenesis InhibitorsApoptosisChick EmbryoPharmacologymedicine.disease_causeMetastasisMaleimidesNeovascularizationGlycogen Synthase Kinase 3Structure-Activity RelationshipNeoplasmsDrug DiscoveryHuman Umbilical Vein Endothelial Cellspolycyclic compoundsmedicineAnimalsHumansProtein kinase AProtein Kinase InhibitorsGSK3BCells CulturedCell ProliferationGlycogen Synthase Kinase 3 betaMolecular StructureNeovascularization PathologicKinaseChemistryCell growthCell CycleVascular Endothelial Growth Factor Receptor-3medicine.diseaseVascular Endothelial Growth Factor Receptor-2Growth Inhibitorsfms-Like Tyrosine Kinase 3Molecular Medicinemedicine.symptomCarcinogenesisJournal of Medicinal Chemistry
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Role of SHP2 for FLT3-dependent proliferation and transformation in 32D cells.

2008

Fms-like tyrosine kinase 3 (FLT3) is a class III receptor tyrosine kinase, which plays a role in proliferation and differentiation of B-cell progenitors, myelomonocytic and dendritic cells, as well as in the maintenance of pluripotent hematopoietic stem cells (reviewed in Stirewalt and Radich,1and Schmidt-Arras et al.2). Recently, FLT3 has received much attention as an important oncoprotein. Mutations in FLT3 that lead to constitutive activation are among the most common molecular lesions found in acute myeloid leukemia.3 The most prevalent type of mutations result in internal tandem duplications (ITD) of amino-acid stretches in the juxtamembrane domain of FLT3. FLT3-ITD is constitutively a…

Cancer ResearchMyeloidProtein Tyrosine Phosphatase Non-Receptor Type 11Biologymedicine.disease_causeReceptor tyrosine kinaseCell LineMicefluids and secretionshemic and lymphatic diseasesmedicineAnimalsHumansRNA Small InterferingCell ProliferationMice Inbred C3Hhemic and immune systemsHematologyHaematopoiesismedicine.anatomical_structureCell Transformation NeoplasticOncologyfms-Like Tyrosine Kinase 3Trk receptorembryonic structuresCancer researchbiology.proteinStem cellSignal transductionCarcinogenesisTyrosine kinaseSignal TransductionLeukemia
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A neoepitope generated by an FLT3 internal tandem duplication (FLT3-ITD) is recognized by leukemia-reactive autologous CD8+ T cells.

2006

Abstract The FLT3 receptor tyrosine kinase is expressed in more than 90% of acute myelogeneous leukemias (AMLs), up to 30% of which carry an internal tandem duplication (ITD) within the FLT3 gene. Although varying duplication sites exist, most FLT3-ITDs affect a single protein domain. We analyzed the FLT3-ITD of an AML patient for encoding HLA class I–restricted immunogenic peptides. One of the tested peptides (YVDFREYEYY) induced in vitro autologous T-cell responses restricted by HLA-A*0101 that were also detectable ex vivo. These peptide-reactive T cells recognized targets transfected with the patient's FLT3-ITD, but not wild-type FLT3, and recognized the patient's AML cells. Our results …

FLT3 Internal Tandem DuplicationMyeloidmedicine.medical_treatmentImmunologyAntigen presentationMolecular Sequence DataHuman leukocyte antigenBiologyCD8-Positive T-LymphocytesIn Vitro TechniquesTransfectionBiochemistryCell LineEpitopesfluids and secretionshemic and lymphatic diseasesCell Line TumorGene DuplicationGene duplicationmedicineCytotoxic T cellHumansAmino Acid SequenceRNA MessengerHLA-A1 AntigenAntigen PresentationHLA-A Antigenshemic and immune systemsCell BiologyHematologyImmunotherapymedicine.diseaseMolecular biologyLeukemiaLeukemia Myeloid Acutemedicine.anatomical_structurefms-Like Tyrosine Kinase 3embryonic structurespsychological phenomena and processesBlood
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AML-associated Flt3 kinase domain mutations show signal transduction differences compared with Flt3 ITD mutations

2005

Activating mutations of Flt3 are found in approximately one third of patients with acute myeloid leukemia (AML) and are an attractive drug target. Two classes of Flt3 mutations occur: internal tandem duplications (ITDs) in the juxtamembrane and point mutations in the tyrosine kinase domain (TKD). We and others have shown that Flt3-ITD induced aberrant signaling including strong activation of signal transducer and activator of transcription 5 (STAT5) and repression of CCAAT/estradiol-binding protein α (c/EBPα) and Pu.1. Here, we compared the signaling properties of Flt3-ITD versus Flt3-TKD in myeloid progenitor cells. We demonstrate that Flt3-TKD mutations induced autonomous growth of 32D ce…

ImmunologyApoptosisBiologymedicine.disease_causeBiochemistryCell Linefluids and secretionsProto-Oncogene Proteinshemic and lymphatic diseasesSTAT5 Transcription FactormedicineAnimalsHumansPoint MutationMyeloid CellsPhosphorylationProtein kinase BProtein kinase CMutationPoint mutationAutophosphorylationIntracellular Signaling Peptides and ProteinsReceptor Protein-Tyrosine Kinaseshemic and immune systemsCell BiologyHematologyMilk ProteinsStaurosporineMolecular biologyProtein Structure TertiaryDNA-Binding ProteinsMuridaefms-Like Tyrosine Kinase 3Leukemia MyeloidTandem Repeat SequencesAcute Diseaseembryonic structuresFms-Like Tyrosine Kinase 3Mutagenesis Site-DirectedTrans-ActivatorsSignal transductionTyrosine kinaseSignal TransductionTranscription FactorsBlood
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