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

摘要 本申请是对特别利益通知(NOSI)的回应，该通知被标识为“非CA-CA- 22-057“。在我们的母公司项目《非洲急性淋巴细胞白血病(ALL)的混合分析》中 美国儿童(海军上将研究；R01CA239701)，我们正在进行混合测绘以识别祖先 可能解释非裔美国人ALL不同风险和不良临床表型的基因组基因座 (Aa)儿童。在这份行政副刊中，有机会刺激或加强全球癌症健康 差异研究，我们提出协同分子流行病学研究来鉴定白血病生物学 在非洲儿童中潜在地低于相同的临床问题(不利于所有表型)的因素。 强调了儿童的沉重负担和有效控制非洲癌症的迫切重要性 由世界卫生组织的全球儿童癌症倡议。建议的目标是 补充性研究项目是利用非洲儿童所有队列作为三角比较者， 与AA有相同的遗传祖先，但缺乏欧洲混血儿，并具有截然不同的 环境免疫挑战，即地方性病毒感染。其目的是为了识别生物 再生障碍性贫血和非洲儿童中所有不利预后因素的基础，可以有针对性地减少 这些人群中的所有生存差距。我们的主要方法是将体细胞、遗传性和 世界各地人群儿童临床差异的环境决定因素；具体目标 目的是：1.确定可能导致所有不良临床表型的细胞遗传学异常 非洲血统的儿童及其与非洲/欧洲基因混合的联系。2.比较 文献中报道的复制遗传单核苷酸变异(SNV)的流行率 与非洲、AA和EA儿童的所有风险和结果有关。3.确定等离子体的特性 非洲ALL儿童中的外源性病毒。

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.