Biomarkers in pediatric versus adult myelodysplastic syndromes

儿童与成人骨髓增生异常综合征的生物标志物

基本信息

批准号：
8892683
负责人：
Michael R. Verneris
金额：
$ 7.6万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8892683
关键词：
Accounting Acute Myelocytic Leukemia Adult Age Alternative Therapies Anemia Apoptosis Applications Grants B-Lymphocytes Biological Assay Biological Markers Biology Blast Cell Blood Blood Cells Blood Platelets Bone Marrow Bone Marrow Transplantation CD34 gene Cell Count Cell Proliferation Cell physiology Cells Characteristics Child Childhood Childhood Leukemia Classification Scheme Clinical Coculture Techniques Cytomegalovirus Data Defect Development Diagnosis Disease Disease Progression Disease-Free Survival Dysmyelopoietic Syndromes Erythrocytes Etiology Fluorescence-Activated Cell Sorting Foundations Frequencies Future Goals Hematopoietic Hematopoietic Neoplasms Hematopoietic Stem Cell Transplantation Hematopoietic stem cells Hypercellular Bone Marrow Immune Immunophenotyping Incidence Ineffective Hematopoiesis Karyotype Knowledge Leukocytes Leukopenia Lymphocyte Lymphoid Malignant Neoplasms Marrow Measures Mediating Myelogenous Natural Killer Cells Outcome Pathology Patients Peripheral Blood Mononuclear Cell Phenotype Population Procedures Production Publishing Recurrence Refractory Refractory Anemia with Excess Blasts in Transformation Refractory anaemia with excess blasts Regulatory T-Lymphocyte Research Sampling Staging Suppressor-Effector T-Lymphocytes T-Lymphocyte T-Lymphocyte and Natural Killer Cell Thrombocytopenia Toxic effect Transplantation Treatment Failure Work World Health Organization advanced disease base burden of illness cell type chemokine clinically relevant cytokine cytopenia cytotoxicity effective therapy improved insight international center leukemia monocyte mortality novel outcome forecast peripheral blood programs public health relevance treatment strategy tumor

项目摘要

DESCRIPTION (provided by applicant): We propose to study pediatric myelodysplastic syndromes (MDS), which are blood cancers characterized by ineffective hematopoiesis. MDS has a much higher incidence in adults, but there is an urgent need for a pediatric approach to diagnosis and treatment: the presentation and clinical course is much more heterogeneous and the disease etiology has not been well studied. Prognosis is poor as progression to advanced disease and leukemia can occur rapidly. Transplantation is the only cure, although treatment failure due to procedure-related mortality and disease recurrence can occur. Alternative therapies are available for adult patients ineligible for transplant, but little study has been don in children. Development of new effective therapies for pediatric MDS requires a better understanding of unique and common hematologic features, which could provide important insights into mechanisms that underlie disease and drive progression. We have obtained 129 pediatric and 100 adult patient samples, along with demographic and MDS pathology details, from the National Marrow Donor Program (NMDP) and Center for International Blood and Marrow Transplant Research (CIBMTR). Further, we have obtained age-matched PBMC controls from 20 adult normal donors and are currently obtaining PBMC from 20 pediatric normal donors. We will: 1) evaluate cells using FACS analysis and established characterization panels including T cell, B cell, natural killer t (NKT) cell and natural killer (NK) cell populatios, monocyte subsets, circulating CD34+ cells, and immune-regulatory populations (e.g., T regulatory cells and myeloid derived suppressor cells); 2) examine lymphocyte and immune-regulatory function in subsets including proliferation, cytokine and chemokine production, degranulation and cytotoxicity. For immune-regulatory populations, measure ability to suppress function performing co-culture assays; and 3) Evaluate clinical correlations (e.g., age, disease status, karyotype, transplant outcome and cytomegalovirus sero-status) with pediatric MDS PBMC phenotypic and functional characteristics and compare to adult MDS patients. Our goal is to comprehensively evaluate and compare pediatric and adult MDS with regard to cell type, function, etc. This work is an important step toward better understanding pediatric MDS biology and developing new treatment strategies.

描述（由申请人提供）：我们建议研究儿童骨髓增生异常综合征（MDS），这是一种以无效造血为特征的血癌，MDS 在成人中的发病率要高得多，但迫切需要一种儿科诊断和治疗方法。：表现和临床病程更加异质性，并且疾病病因尚未得到充分研究，因为进展为晚期疾病并且移植是唯一的选择。尽管对于不适合移植的成年患者可能会出现因手术相关的死亡率和疾病复发而导致治疗失败的情况，但针对儿童 MDS 的新有效疗法的开发还需要更好的了解。我们从国家骨髓捐赠计划 (NMDP) 和 MDS 获得了 129 名儿童和 100 名成人患者样本，以及人口统计和 MDS 病理学详细信息。此外，我们已从 20 名成人正常捐献者中获得了年龄匹配的 PBMC 对照，目前正在从 20 名儿童正常捐献者中获得 PBMC，我们将：1) 使用 FACS 分析评估细胞并建立。表征面板，包括 T 细胞、B 细胞、自然杀伤 T (NKT) 细胞和自然杀伤 (NK) 细胞群、单核细胞亚群、循环 CD34+ 细胞和免疫调节细胞群（例如，T 调节细胞和骨髓来源的抑制细胞）；2) 检查亚群中的淋巴细胞和免疫调节功能，包括增殖、细胞因子和趋化因子的产生、脱颗粒和细胞毒性。培养测定；和 3) 评估与儿科 MDS 的临床相关性（例如年龄、疾病状态、核型、移植结果和巨细胞病毒血清状态） PBMC 表型和功能特征以及与成人 MDS 患者的比较我们的目标是全面评估和比较儿童和成人 MDS 的细胞类型、功能等。这项工作是更好地了解儿科 MDS 生物学和开发新治疗方法的重要一步。策略。