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

摘要 本申请是为了响应被标识为“NOT-CA-”的特别利益通知（NOSI）而提交的。 22-057”。在我们题为“非洲急性淋巴细胞白血病（ALL）的混合物分析”的母项目中， 美国儿童（ADMIRAL研究; R 01 CA 239701），我们正在进行混合物图谱以识别祖先 可能解释非裔美国人ALL不同风险和不利临床表型的基因组位点 (AA)孩子在这个行政补充机会，刺激或加强全球癌症健康 差异研究，我们建议协同分子流行病学研究，以确定白血病生物学 这些因素可能导致非洲儿童出现相同的临床问题（不利的ALL表型）。 强调了儿童ALL的高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 补充研究项目是利用这个非洲儿童ALL队列作为三角比较， 与AA共享遗传祖先，但缺乏欧洲混合物，并具有明显不同的景观， 环境免疫挑战，即地方性病毒感染。其目的是识别生物 AA和非洲儿童中不利ALL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异。我们的总体方法是描述躯体的，遗传的， 世界人群中儿童ALL临床差异的环境决定因素; 1.确定细胞遗传学异常可能是不利的ALL临床表型的基础， 非洲血统的儿童及其与非洲/欧洲遗传混合物的关系。2.比较 复制的遗传性单核苷酸变异（SNV）的患病率，在文献中报道， 与非洲、AA和EA儿童的ALL风险和结局相关。3.表征血浆 非洲ALL患儿的外源性病毒组。

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.