Novel Biomarkers to Risk-Stratify AML Patients with NPM1^Pos/FLT3-IT^Neg Genotype
对具有 NPM1^Pos/FLT3-IT^Neg 基因型的 AML 患者进行风险分层的新型生物标志物
基本信息
- 批准号:9452035
- 负责人:
- 金额:$ 58.03万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-04-01 至 2021-03-31
- 项目状态:已结题
- 来源:
- 关键词:Acute Myelocytic LeukemiaAddressAdultAgeBioinformaticsBiological AssayBiological MarkersBlast CellCharacteristicsChildClassificationClinicalComplexCoupledCytogeneticsDNADNA sequencingDataData SetDevelopmentDiagnosticDiseaseDisease remissionEvaluationFLT3 geneFlow CytometryFutureGenesGenetic TranscriptionGenomeGenomicsGenotypeGuidelinesHematopoietic NeoplasmsHeterogeneityInformation TechnologyLaboratoriesLeadLettersMass Spectrum AnalysisMessenger RNAMethodsMicroRNAsModelingMolecularMutationNPM1 geneNatureOutcomePatientsPediatric Oncology GroupPerformancePopulationProbabilityPrognostic FactorPrognostic MarkerProteinsProteomeProteomicsRNARecommendationRegression AnalysisRelapseResearchRiskRisk stratificationSamplingSouthwest Oncology GroupTechniquesTechnologyThe Cancer Genome AtlasTranscriptUniversitiesWashingtonbasebiomedical informaticsclinical practicecostdesignimprovedinnovationliquid chromatography mass spectrometrymolecular markermutational statusnew therapeutic targetnovelnovel markeroutcome forecastpatient populationpatient stratificationprognosticprognostic significanceprotein biomarkerspublic health relevancerepositoryresponsespecific biomarkersstatisticssynergismtooltranscriptometranscriptome sequencingtreatment guidelines
项目摘要
DESCRIPTION (provided by applicant): Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies, with NPM1 mutations and FLT3/ITDs being two of the most prognostic biomarkers for this disease. Patients with the NPM1Pos/FLT3-ITDNeg genotype account for approximately 25% of de novo AML cases and are currently classified as better-risk. However, approximately 40% of these patients do not obtain a remission or relapse within 2 years. We hypothesize that AML blasts with the NPM1Pos/FLT3-ITDNeg genotype harbor additional prognostic biomarkers that can be used to more accurately risk-stratify patients with this genotype. Therefore, we will examine viable leukemic blasts from AML patients with this genotype to identify novel genomic, transcriptional and proteomic prognostic biomarkers. We will then develop risk-stratification models incorporating these biomarkers and other prognostic factors and validate these risk-stratification models in an independent population of patients. Specific Aim 1. Identify novel molecular biomarkers associated with prognosis in AML patients with the NPM1Pos/FLT3-ITDNeg genotype. Viable AML blasts will be isolated from patients with intermediate-risk cytogenetics and the NPM1Pos/FLT3-ITDNeg genotype (N=131). Targeted DNA sequencing, global RNA sequencing, and mass spectrometry employing an innovative approach will be used to identify DNA, transcript, and protein biomarkers that are associated with clinical outcomes. Regression analyses, integrating molecular data and other prognostic factors, will be used to identify the most informative biomarkers, and these prognostic biomarkers will be incorporated into risk-stratification models for estimating the probability of overall survival and
relapse-free survival. Specific Aim 2. Validate the ability of the biomarkers from Specific Aim 1 to more accurately risk-stratify AML patients with the NPM1Pos/FLT3-ITDNeg genotype. Targeted assays for biomarkers in the risk- stratification models will be developed. The design specifics of
these assays will depend upon the characteristics of the target and rely upon previously developed and optimized technology. We will then examine the biomarkers and risk-stratification models in an independent population of AML patients with this genotype (N = 194). The performance of the risk-stratification model(s) employing will be evaluated by estimating AUCs and c-statistics. The results from this proposal will likely lead to the development of improved risk-stratification model(s) for AML patients with the NPM1Pos/FLT3-ITDNeg genotype. In addition, identified biomarkers may have prognostic significance beyond this genotype, and future studies will examine the generalizability of these findings to other AML subpopulations. Furthermore, the comprehensive nature of these studies, spanning from the genome to the proteome, will advance our understanding of the complex interactions among prognostic biomarkers, leading to more informed and potentially directive approaches for future biomarker research.
项目成果
期刊论文数量(0)
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{{ truncateString('DEREK L STIREWALT', 18)}}的其他基金
Novel Biomarkers to Risk-Stratify AML Patients with NPM1^Pos/FLT3-IT^Neg Genotype
对具有 NPM1^Pos/FLT3-IT^Neg 基因型的 AML 患者进行风险分层的新型生物标志物
- 批准号:
9899941 - 财政年份:2016
- 资助金额:
$ 58.03万 - 项目类别:
Novel Biomarkers to Risk-Stratify AML Patients with NPM1^Pos/FLT3-IT^Neg Genotype
对具有 NPM1^Pos/FLT3-IT^Neg 基因型的 AML 患者进行风险分层的新型生物标志物
- 批准号:
9105139 - 财政年份:2016
- 资助金额:
$ 58.03万 - 项目类别:
Discovery and Optimization of AML Prognostic Biomarkers
AML 预后生物标志物的发现和优化
- 批准号:
8625275 - 财政年份:2012
- 资助金额:
$ 58.03万 - 项目类别:
Discovery and Optimization of AML Prognostic Biomarkers
AML 预后生物标志物的发现和优化
- 批准号:
9024460 - 财政年份:2012
- 资助金额:
$ 58.03万 - 项目类别:
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