Search results for "INTERNAL TANDEM DUPLICATION"

showing 9 items of 9 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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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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Next-Generation Sequencing (NGS)-Based Measurable Residual Disease (MRD) Monitoring in Acute Myeloid Leukemia with FLT3 Internal Tandem Duplication (…

2020

Background: FLT3-ITD occurs in ~25% of adult AML patients (pts) and is associated with poor prognosis. MRD monitoring is of high prognostic relevance, but restricted to certain AML subtypes. FLT3-ITD represents an attractive target for MRD monitoring in particular in pts treated with a tyrosine kinase inhibitor. FLT3-ITD MRD monitoring is hampered by the broad heterogeneity of ITD length and insertion site (IS). NGS may overcome these limitations offering the opportunity for MRD monitoring in FLT3-ITD+ AML. Aims: To validate our recently established NGS-based FLT3-ITD MRD assay in a defined cohort of FLT3-ITD+ AML pts treated within the AMLSG16-10 trial (NCT01477606) combining intensive che…

FLT3 Internal Tandem Duplicationbusiness.industryImmunologyMyeloid leukemiaCell BiologyHematologyDiseaseBiochemistryDNA sequencingchemistry.chemical_compoundchemistryCancer researchMedicineMidostaurinbusinessFlt3 itdBlood
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Prognostic value of FLT3 mutations in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemother…

2011

Background Fms-like tyrosine kinase-3 (FLT3) gene mutations are frequent in acute promyelocytic leukemia but their prognostic value is not well established. Design and Methods We evaluated FLT3-internal tandem duplication and FLT3-D835 mutations in patients treated with all-trans retinoic acid and anthracycline-based chemotherapy enrolled in two subsequent trials of the Programa de Estudio y Tratamiento de las Hemopatias Malignas (PETHEMA) and Hemato-Oncologie voor Volwassenen Nederland (HOVON) groups between 1996 and 2005. Results FLT3-internal tandem duplication and FLT3-D835 mutation status was available for 306 (41%) and 213 (29%) patients, respectively. Sixty-eight (22%) and 20 (9%) pa…

MaleAIDA PROTOCOLGene mutationmedicine.disease_causeGastroenterologyLeukemia Promyelocytic AcuteRESIDUAL DISEASEhemic and lymphatic diseasesMOLECULAR SUBTYPESChildanthracyclinesMutationRemission InductionFLT3 mutationshemic and immune systemsHematologyMiddle AgedPrognosisall-trans retinoic acidLeukemiaTreatment Outcomeembryonic structuresFemaleTandem exon duplicationmedicine.drugAcute promyelocytic leukemiaAdultmedicine.medical_specialtyAdolescentAntineoplastic AgentsTretinoinACUTE MYELOID-LEUKEMIABiologyYoung AdultQUALITY-CONTROLTretinoinPOOR-PROGNOSISInternal medicinemedicineCoagulopathyHumansAgedprognostic factorsOriginal Articlesacute promyelocytic leukemiamedicine.diseaseSurvival AnalysisINTERNAL TANDEM DUPLICATIONRISK-ADAPTED TREATMENTPML/RAR-ALPHAfms-Like Tyrosine Kinase 3Fms-Like Tyrosine Kinase 3ImmunologyPETHEMA GROUPMutation
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Prognostic Impact of Mutant to Wild-Type Ratio and Insertion Site in Acute Myeloid Leukemia with FLT3 Internal Tandem Duplication

2012

Abstract Abstract 785 Background: FLT3 internal tandem duplications (FLT3-ITD) occur in about 25% of acute myeloid leukemia (AML), are associated with cooperating gene mutations (NPM1, DNMT3A), and confer an adverse prognosis. Several studies have indicated that the unfavorable impact of FLT3-ITD is influenced by a number of factors, such as the mutant to wild-type ratio (allelic ratio), insertion site of FLT3-ITD in the beta1 sheet of the tyrosine kinase domain 1, and the molecular background of cooperating mutations. Aims: To evaluate the relative impact of FLT3-ITD allelic ratio and insertion site, as well as cooperating genetic lesions on prognosis and treatment decision making in a lar…

OncologyAcute promyelocytic leukemiaFLT3 Internal Tandem Duplicationmedicine.medical_specialtyNPM1business.industrymedicine.medical_treatmentImmunologyMyeloid leukemiaCell BiologyHematologyHematopoietic stem cell transplantationGene mutationmedicine.diseaseBiochemistrySurgeryQuartilehemic and lymphatic diseasesInternal medicinemedicinebusinesspsychological phenomena and processesNeoadjuvant therapyBlood
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Impact of NPM1/FLT3-ITD genotypes defined by the 2017 European LeukemiaNet in patients with acute myeloid leukemia

2020

Contains fulltext : 218279.pdf (Publisher’s version ) (Open Access) Patients with acute myeloid leukemia (AML) harboring FLT3 internal tandem duplications (ITDs) have poor outcomes, in particular AML with a high (>/=0.5) mutant/wild-type allelic ratio (AR). The 2017 European LeukemiaNet (ELN) recommendations defined 4 distinct FLT3-ITD genotypes based on the ITD AR and the NPM1 mutational status. In this retrospective exploratory study, we investigated the prognostic and predictive impact of the NPM1/FLT3-ITD genotypes categorized according to the 2017 ELN risk groups in patients randomized within the RATIFY trial, which evaluated the addition of midostaurin to standard chemotherapy. The 4 …

OncologyPROBABILITIESMalePROGNOSISCancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2]NPM1 MUTATIONBiochemistryEuropean LeukemiaNetchemistry.chemical_compoundALLELIC RATIOAMLRisk FactorsGene Duplicationhemic and lymphatic diseasesMidostaurinFLT3Myeloid NeoplasiaHematopoietic Stem Cell TransplantationMyeloid leukemiaNuclear ProteinsHematologyCHEMOTHERAPYMiddle AgedPrognosisChemotherapy regimenEuropeLeukemia Myeloid Acutemedicine.anatomical_structureTreatment OutcomeTandem Repeat SequencesFemaleNucleophosminmedicine.medical_specialtyNPM1GenotypeImmunologyYOUNGER ADULTSInternal medicineWhite blood cellmedicineNORMAL CYTOGENETICSHumansGenetic Predisposition to DiseaseProportional Hazards ModelsProportional hazards modelbusiness.industryCell BiologyINTERNAL TANDEM DUPLICATIONTransplantationchemistryfms-Like Tyrosine Kinase 3Multivariate AnalysisbusinessSettore MED/15 - Malattie del Sangue
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Synthesis of 2H-Imidazo[2',1':2,3] [1,3]thiazolo[4,5-e]isoindol-8-yl-phenylureas with promising therapeutic features for the treatment of acute myelo…

2022

Despite progressive advances in understanding the molecular biology of acute myeloid leukemia (AML), the conventional therapeutic approach has not changed substantially, and the outcome for most patients is poor. Thus, continuous efforts on the discovery of new compounds with improved features are required. Following a multistep sequence, we have identified a new tetracyclic ring system with strong antiproliferative activity towards several haematological cell lines. The new compounds possess structural properties typical of inactive-state-binding kinase inhibitors and are structurally related to quizartinib which is known as type-II tyrosine kinase inhibitor. In particular, the high activi…

PharmacologyFMS-like tyrosine kinase 3 (FLT3)FLT3/ITD3][13]thiazolo[4Organic Chemistry2H-imidazo [2′1':23][13]thiazolo[45-e]isoindol-8-yl-phenylureas2H-imidazo [2′1':23][13]thiazolo[45-e]isoindol-8-yl-phenylureas; Acute myeloid leukemia (AML); FLT3/ITD; FMS-like tyrosine kinase 3 (FLT3); Internal tandem duplication (ITD)ApoptosisGeneral Medicine2H-imidazo [2′Leukemia Myeloid AcuteMiceInternal tandem duplication (ITD)fms-Like Tyrosine Kinase 35-e]isoindol-8-yl-phenylureasCell Line TumorDrug DiscoveryMutationAcute myeloid leukemia (AML)AnimalsHumansProtein Kinase Inhibitors1':2European journal of medicinal chemistry
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Sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with FLT3-internal tandem duplication mutat…

2020

PURPOSE Despite undergoing allogeneic hematopoietic stem cell transplantation (HCT), patients with acute myeloid leukemia (AML) with internal tandem duplication mutation in the FMS-like tyrosine kinase 3 gene ( FLT3-ITD) have a poor prognosis, frequently relapse, and die as a result of AML. It is currently unknown whether a maintenance therapy using FLT3 inhibitors, such as the multitargeted tyrosine kinase inhibitor sorafenib, improves outcome after HCT. PATIENTS AND METHODS In a randomized, placebo-controlled, double-blind phase II trial (SORMAIN; German Clinical Trials Register: DRKS00000591), 83 adult patients with FLT3-ITD–positive AML in complete hematologic remission after HCT were r…

SorafenibFLT3 Internal Tandem DuplicationCancer ResearchMyeloidbusiness.industrymedicine.medical_treatmentMyeloid leukemiaHematopoietic stem cell transplantationmedicine.diseaseTransplantationLeukemiamedicine.anatomical_structureOncologyhemic and lymphatic diseasesmedicineCancer researchNeoplasmbusinessmedicine.drug
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