Analysis of Developmental Arrest and Treatment Resistance in High-risk T-ALL
高危 T-ALL 发育停滞和治疗抵抗分析
基本信息
- 批准号:10387279
- 负责人:
- 金额:$ 5.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-01-21 至 2025-01-20
- 项目状态:未结题
- 来源:
- 关键词:AccountingAcute Lymphocytic LeukemiaAcute Myelocytic LeukemiaAcute leukemiaAddressAutomobile DrivingB-LymphocytesBiologic CharacteristicBiologicalBiological AssayBiological ModelsBone MarrowCD32 AntigensCell LineCell surfaceCellsCellular AssayCharacteristicsChildhood LeukemiaChromatinClinicalClinical TrialsClustered Regularly Interspaced Short Palindromic RepeatsCommon Acute Lymphoblastic LeukemiaComputer AnalysisCoupledDataData AnalysesDevelopmentDiagnosisDisease remissionEarly treatmentEnrollmentEpigenetic ProcessEquilibriumFlow CytometryGene ExpressionGenesGeneticGenomicsGoalsGrantHematopoietic stem cellsImmunophenotypingIn complete remissionInferiorKnowledgeLeadLymphoidLymphoid CellMalignant Childhood NeoplasmMalignant NeoplasmsMapsMeasurementModelingMolecularMorbidity - disease rateMutationMyelogenousMyeloid CellsOutcomePathway interactionsPatientsPharmacological TreatmentPhenotypePlant RootsPopulationPostdoctoral FellowProcessRelapseResidual NeoplasmSamplingSmall Interfering RNAStainsSurfaceT-Cell DevelopmentT-LymphocyteTestingTherapeuticThymus GlandTransposaseTreatment FailureUnited States National Institutes of HealthWorkbasecancer diagnosiscarcinogenesiscell typechemotherapycohortconventional therapyhigh riskimprovedmortalitymultiple omicsmyeloid cell developmentnovelnovel therapeutic interventionprogenitorprognosticprognostic signatureprospectiveresponserisk stratificationsingle-cell RNA sequencingstemstem-like celltargeted treatmenttherapy resistanttooltranscriptome sequencingtranscriptomicstreatment responsevalidation studies
项目摘要
Project Summary
Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, accounting for nearly 1 in 3 new
pediatric cancer diagnoses. Though mortality and morbidity associated with common ALL subtypes have
drastically improved as a result of advances in chemotherapy and risk stratification, high rates of treatment failure
persist in understudied subtypes of ALL, such as early T-cell precursor acute lymphoblastic leukemia (ETP-ALL).
ETP-ALL patients fail the first month of chemotherapy at 7.7x the rate of non-ETP ALL patients and are twice as
likely to have detectable residual disease at end of induction chemotherapy. We hypothesize that these striking
differences in response to treatment are intrinsically rooted in biological characteristics of ETP-ALL, which can
be further revealed using high-throughput measurement tools, such as single-cell genomics.
The completion of COG’s AALL00344 clinical trial, which enrolled 325 ETP-ALL patients, represents an exciting
opportunity to improve our understanding of ETP-ALL and identify the biological reasons for treatment failure. In
Aim 1, we will use single cell transcriptomics and single cell chromatin accessibility to investigate clonal diversity,
transcriptomic features and epigenetic signatures in 30 patients with ETP-ALL. We will seek to place ETP-ALL
blasts in context of healthy T-cell development and other pediatric leukemias. In Aim 2, we will compare ETP-
ALL patients based on clinical response and use patient-specific xenograph models to functionally perturb genes
and pathways enriched in non-responding patients. Our project is poised to synergize with bulk sequencing data
being generated for 325 ETP-ALL patients through an NIH X01 grant (HD100702-01), specifically due to our
ability to deconvolute bulk sequencing data using subclone-specific signatures discovered in single cell data.
We believe the proposed work can help to elucidate the genetic drivers of ETP-ALL and identify targets and cell
populations associated with treatment failure, thus significantly impacting the diagnosis and treatment of ETP-
ALL.
项目总结
项目成果
期刊论文数量(0)
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Jason Xu其他文献
Jason Xu的其他文献
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{{ truncateString('Jason Xu', 18)}}的其他基金
Analysis of Developmental Arrest and Treatment Resistance in High-risk T-ALL
高危 T-ALL 发育停滞和治疗抵抗分析
- 批准号:
10573148 - 财政年份:2022
- 资助金额:
$ 5.18万 - 项目类别:
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