Admixture analysis of acute lymphoblastic leukemia in African American children: the ADMIRAL Study

非裔美国儿童急性淋巴细胞白血病的混合分析：ADMIRAL 研究

• 批准号: 10626271
• 负责人: Joseph Lubega
• 金额: $ 19.76万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10626271
• 关键词: Acute Lymphocytic Leukemia; Administrative Supplement; Admixture; Africa; African; African American; African ancestry; American; Biological; Biology; Cancer Control; Cell Lineage; Child; Childhood; Childhood Acute Lymphocytic Leukemia; Childhood Leukemia; Chromosome abnormality; Cities; Clinical; Clinical Data; Clinical Research; Collection; Complement; Cytogenetics; DNA; Data Set; Enrollment; Environment; Epidemiology; European; Fluorescent in Situ Hybridization; Gene Frequency; Genetic; Genomics; Genotype; Goals; Health Disparities Research; High Prevalence; Immune; Inherited; Institutional Review Boards; Literature; Low Prevalence; Malignant Childhood Neoplasm; Malignant Neoplasms; Molecular Epidemiology; Newly Diagnosed; Outcome; Parents; Pathologic; Pattern; Pediatric Hospitals; Phenotype; Plasma; Population; Prevalence; Prognosis; Prognostic Factor; Protocols documentation; Redwood; Relative Risks; Reporting; Research; Research Project Grants; Risk; Risk Factors; Single Nucleotide Polymorphism; T-Lymphocyte; Testing; Texas; Tissues; Uganda; Viral Load result; Virus; Virus Diseases; World Health Organization; admixture mapping; cancer health disparity; clinical phenotype; cohort; disparity elimination; early childhood; epidemiology study; genomic locus; high risk; improved; innovation; interest; leukemia; parent project; prognostic significance; programs; prospective; recruit; response; survival disparity; tumor; virome

Abstract This application is being submitted in response to the Notice of Special Interest (NOSI) identified as “NOT-CA- 22-057”. In our parent project titled “Admixture analysis of acute lymphoblastic leukemia (ALL) in African American children (ADMIRAL Study; R01CA239701), we are performing admixture mapping to identify ancestral genomic loci that may account for differential risk and unfavorable clinical phenotypes of ALL in African American (AA) children. In this Administrative Supplement Opportunity to Stimulate or Strengthen Global Cancer Health Disparities Research, we propose synergistic molecular epidemiology research to identify leukemia biology factors that potentially underly the same clinical problem (unfavorable ALL phenotypes) among children in Africa. The high burden of childhood ALL and urgent importance to effectively control the cancer in Africa is highlighted by the World Health Organization’s Global Initiative for Childhood Cancer. The goal of the proposed supplemental research project is to leverage this African childhood ALL cohort as a triangulating comparator that shares genetic ancestry with AA but lacks European admixture and has a distinctively different landscape of environmental immune challenges, namely, endemic viral infections. The purpose is to identify the biological underpinnings of unfavorable ALL prognostic factors in AA and African children that can be targeted to reduce ALL survival disparities in these populations. Our overarching approach is to characterize somatic, inherited, and environmental determinants of clinical differences in childhood ALL among world populations; the Specific Aims are to: 1. Identify the cytogenetic abnormalities that may underpin unfavorable ALL clinical phenotypes among children of African ancestry and their association with African/European genetic admixture. 2. Compare the prevalence of replicated inherited single nucleotide variants (SNVs) that are reported in the literature to be associated with ALL risk and outcomes among African, AA and EA children. 3. Characterize the plasma exogenous virome in children with ALL in Africa.

抽象的 本申请是为了响应被标识为“NOT-CA-”的特殊利益通知 (NOSI) 而提交的。 22-057”。在我们的母项目“非洲急性淋巴细胞白血病 (ALL) 的混合分析”中。 美国儿童（ADMIRAL 研究；R01CA239701），我们正在执行混合映射来识别祖先 可能解释非裔美国人 ALL 的差异风险和不利临床表型的基因组位点 (AA) 儿童。 差异研究，我们提出协同分子流行病学研究来识别白血病生物学 非洲儿童中可能存在相同临床问题（不利的所有表型）的因素。 强调了非洲儿童 ALL 的沉重负担和有效控制癌症的紧迫性 世界卫生组织全球儿童癌症倡议提出的目标。 补充研究项目是利用这个非洲儿童 ALL 队列作为三角测量比较器 基因与 AA 有共同血统，但缺乏欧洲混血，并且具有截然不同的景观 环境免疫挑战，即地方性病毒感染，目的是识别生物。 AA 和非洲儿童所有不利预后因素的基础，可以有针对性地减少 我们的总体方法是描述这些人群的所有生存差异的体细胞特征、遗传特征和特征。 世界人口中儿童 ALL 临床差异的环境决定因素； 目的是： 1. 识别可能导致所有不利临床表型的细胞遗传学异常 非洲血统的孩子及其与非洲/欧洲基因混合的关系 2. 比较。 文献报道复制遗传性单核苷酸变异（SNV）的普遍性 与非洲、AA 和 EA 儿童的 ALL 风险和结果相关 3. 表征血浆。 非洲 ALL 儿童的外源病毒组。