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

• 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
• 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

 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（由适用提供）：我们建议研究小儿骨髓增生综合征（MDS），它们是以无效造血作用为特征的血液癌。 MD在成人中的发病率要高得多，但是迫切需要采用儿科方法来诊断和治疗：表现和临床过程更加异质，疾病病因学并不是很好的研究。预后很差，因为进展为晚期疾病，白血病可能会迅速发生。移植是唯一的治疗方法，尽管可能会由于手术相关的死亡率和疾病复发而导致的治疗失败。对于不符合移植资格的成年患者，可用于替代疗法，但对儿童的研究很少。开发针对小儿MDS的新有效疗法需要更好地了解独特和常见的血液学特征，这可以为基于疾病和推动进展的机制提供重要的见解。我们从国家骨髓供体计划（NMDP）和国际血液和骨髓移植研究中心（CIBMTR）获得了129个小儿和100个成年患者样本，以及人口统计和MDS病理细节。此外，我们已经从20个成年正常供体中获得了年龄匹配的PBMC对照，目前正在从20个小儿普通供体中获得PBMC。 WILL：1）使用FACS分析和既定表征面板评估细胞，包括T细胞，B细胞，天然杀伤剂T（NKT）细胞和天然杀伤（NK）细胞群，单核细胞亚群，循环CD34+细胞以及免疫调节群体（例如，调节性细胞和髓样细胞）； 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产生，脱粒和细胞毒性。对于免疫调节人群，测量能力抑制功能表现共同文化评估的能力； 3）用小儿MDS PBMC表型和功能特征和与成人MDS患者相比，评估临床相关性（例如，年龄，疾病状况，核型，核型，移植结果和巨细胞病毒血清状态），并与儿科MDS PBMC表型和功能特征相比。我们的目标是在细胞类型，功能等方面全面评估和比较儿科和成人MD。这项工作是更好地理解小儿MDS生物学并制定新的治疗策略的重要一步。