Biomarker Discovery in Chronic Graft-vs-Host Disease

慢性移植物抗宿主病的生物标志物发现

基本信息

项目摘要

DESCRIPTION (provided by applicant): Chronic graft-versus-host disease (cGVHD) occurs in 50-70% of patients following allogeneic hematopoietic stem cell transplantation (HSCT) and is a major cause of morbidity and mortality. The clinical manifestations of cGVHD are diverse and variable, and the diagnosis, staging and assessment of response to therapeutic interventions have been difficult to standardize. There are no signs or symptoms or diagnostic tools that predict the development or severity of cGVHD, or the need for immune suppression therapy. The goal of this proposal is to address these unmet needs by identifying novel biomarkers that are associated with the onset and severity of cGVHD. The initial phase of study will consist of a parallel discovery strategy that employs a genome-wide analysis of transcriptional changes in peripheral blood mononuclear cells (PBMC) together with a high-resolution, high-sensitivity quantitative proteomic analysis to identify informative proteins in plasma that correlate with disease activity. These transcriptional changes and proteins will be prioritized to develop a list of candidates for second phase validation studies to confirm and further define a panel of markers that together provide high sensitivity and specificity for the diagnosis of cGVHD and the prediction of severity and/or treatment response. Aim 1 of this study is to identify novel biomarkers in peripheral blood for the diagnosis of cGVHD using dual approaches: 1a) analysis of global gene expression and alternate splicing in mononuclear leucocytes; and 1b) quantitative in-depth profiling of circulating proteins in plasma. The transcriptional analysis will be performed on PBMC using the Affymetrix Human Exon 1.0 ST array, and the proteomic analysis will be performed on plasma by mass spectrometry. Aim 2 will focus on the validation of candidate biomarkers identified in an independent, multicenter cohort study of cGVHD. Candidate genes and alternate splice variants will be validated by PCR-based assays, and candidate proteins will be validated by antibody-based assays. This application is submitted in response to RFA-HL-08-001, titled "Ancillary Studies in Clinical trials (R01)." We are proposing a biomarker discovery and validation project that is focused on cGVHD occurring after allo HSCT. The subjects for this study, cases and controls, will be enrolled in a separate NIH funded multi-center study titled "Improving outcomes assessment in chronic GVHD" (R01-CA118953; Dr. Stephanie Lee, PI). Participating Centers include the Dana-Farber Cancer Institute (DFCI), the Seattle Cancer Care Alliance (SCCA)/Fred Hutchinson Cancer Research Center (FHCRC), Stanford University and the University of Minnesota. Total enrollment across the sites will reach 336 incident and 336 prevalent cGVHD cases. Patients will be followed for three years, and systematically evaluated for cGVHD status and response to cGVHD therapy. Chronic graft-versus-host disease (cGVHD) occurs in 50-70% of patients following allogeneic hematopoietic stem cell transplantation (HSCT) and is a major cause of morbidity and mortality. As the utilization of HSCT and number of HSCT survivors increases, the issue of cGVHD becomes a greater concern not only to patients and their families but also to the specialized physicians and health care facilities responsible for their care. The studies proposed here are aimed at improving methods for the diagnosis of cGVHD, monitoring disease activity and the effectiveness of cGVHD therapy. These studies may also yield insights into the underlying disorders responsible for cGVHD and thereby suggest new treatment strategies. (End of Abstract)
描述(由申请人提供):

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A combined biomarker and clinical panel for chronic graft versus host disease diagnosis.
用于慢性移植物与宿主疾病诊断的合并生物标志物和临床面板。
  • DOI:
    10.1002/cjp2.58
  • 发表时间:
    2017-01
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Pidala J;Sigdel TK;Wang A;Hsieh S;Inamoto Y;Martin PJ;Flowers ME;Hansen JA;Lee SJ;Sarwal MM
  • 通讯作者:
    Sarwal MM
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John Andrew Hansen其他文献

John Andrew Hansen的其他文献

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{{ truncateString('John Andrew Hansen', 18)}}的其他基金

Whole Genome Association Analysis of Hematopoietic Cell Transplant (HCT) Outcome
造血细胞移植 (HCT) 结果的全基因组关联分析
  • 批准号:
    8212026
  • 财政年份:
    2011
  • 资助金额:
    $ 44万
  • 项目类别:
Whole Genome Association Analysis of Hematopoietic Cell Transplant (HCT) Outcome
造血细胞移植 (HCT) 结果的全基因组关联分析
  • 批准号:
    8022984
  • 财政年份:
    2011
  • 资助金额:
    $ 44万
  • 项目类别:
Program Administration
项目管理
  • 批准号:
    8309106
  • 财政年份:
    2011
  • 资助金额:
    $ 44万
  • 项目类别:
Whole Genome Association Analysis of Hematopoietic Cell Transplant (HCT) Outcome
造血细胞移植 (HCT) 结果的全基因组关联分析
  • 批准号:
    8603178
  • 财政年份:
    2011
  • 资助金额:
    $ 44万
  • 项目类别:
Regulatory T Cells in Graft-versus-Host Disease
移植物抗宿主病中的调节性 T 细胞
  • 批准号:
    8309105
  • 财政年份:
    2011
  • 资助金额:
    $ 44万
  • 项目类别:
Whole Genome Association Analysis of Hematopoietic Cell Transplant (HCT) Outcome
造血细胞移植 (HCT) 结果的全基因组关联分析
  • 批准号:
    8424322
  • 财政年份:
    2011
  • 资助金额:
    $ 44万
  • 项目类别:
Whole Genome Association Analysis of Hematopoietic Cell Transplant (HCT) Outcome
造血细胞移植 (HCT) 结果的全基因组关联分析
  • 批准号:
    9389761
  • 财政年份:
    2011
  • 资助金额:
    $ 44万
  • 项目类别:
Program Administration
项目管理
  • 批准号:
    7676418
  • 财政年份:
    2009
  • 资助金额:
    $ 44万
  • 项目类别:
Regulatory T Cells in Graft-versus-Host Disease
移植物抗宿主病中的调节性 T 细胞
  • 批准号:
    7676416
  • 财政年份:
    2009
  • 资助金额:
    $ 44万
  • 项目类别:
Biomarker Discovery in Chronic Graft-vs-Host Disease
慢性移植物抗宿主病的生物标志物发现
  • 批准号:
    7881588
  • 财政年份:
    2008
  • 资助金额:
    $ 44万
  • 项目类别:

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