Prevalence and persistence of the ETV6/RUNX1 pre-leukemic clone

ETV6/RUNX1 白血病前克隆的患病率和持续性

• 批准号: 10594288
• 负责人: Erin Marcotte
• 金额: $ 94.04万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10594288
• 关键词: Acute Lymphocytic Leukemia; Age; Appearance; Birth; Blood; Blood Cells; Blood specimen; California; Case/Control Studies; Cells; Child; Childhood; Childhood Acute Lymphocytic Leukemia; Childhood Leukemia; Clinical; Cohort Studies; Data; Descriptive Epidemiology; Development; Disease; Dryness; Epidemiology; Ethnic Population; Etiology; Event; Fostering; Gene Fusion; Genetic; Genetic Diseases; Genomics; Goals; Individual; Infant; Investments; Knowledge; Laboratories; Longitudinal Studies; Malignant Childhood Neoplasm; Malignant Neoplasms; Methods; Michigan; Monitor; Neonatal Screening; New Hampshire; Newborn Infant; Participant; Patients; Pediatric epidemiology; Population; Predictive Factor; Preleukemia; Prevalence; Prevention; RNA; RNA-Directed DNA Polymerase; RUNX1 gene; Recontacts; Risk; Risk Estimate; Risk Factors; Spottings; Time; Translating; United States National Institutes of Health; Work; cancer diagnosis; case control; clinical application; cohort; design; detection method; digital; early childhood; epidemiology study; ethnic diversity; genetic risk assessment; high risk; high risk population; in utero; innovation; leukemia; novel; population based; prenatal; racial population; risk prediction; screening; t(12; 21)(p13; q22)

Abstract Leukemia is the most common childhood cancer and represents approximately one third of all cancer diagnoses among children age 0-14. There is strong evidence that acute lymphoblastic leukemia (ALL), the most common type of leukemia in children, is initiated in utero. The ETV6/RUNX1 gene fusion, which is considered an early initiating event in the development of ALL, is present at birth in some children who later develop ALL. Children born with these leukemia-specific translocation in blood cells have pre-leukemia, and there is a need to define the epidemiology of pre-leukemia and identify the factors that contribute to pre-leukemia persistence and progression to ALL. We have developed a robust new method for detection of ETV6/RUNX1 pre-leukemia which uses newborn blood spots. We propose to use this method to: 1) examine the newborn blood spots of 500 children who later developed leukemia and from 3000 healthy children who did not develop leukemia to identify the determinants of pre-leukemia at birth; 2) estimate the risk of childhood ALL given pre-leukemia at birth; and 3) evaluate how long pre-leukemia persists in childhood using both newborn blood spots and, from the same cohort of children, blood samples collected over time within early childhood. Together, these goals will allow us to determine how many children with ALL are born with the leukemia gene fusion; what factors predict pre- leukemia at birth; how many children who never develop leukemia are born with the gene fusion; and how long the gene fusion persists in childhood. Establishing the true population prevalence and determinants of ETV6/RUNX1 gene fusion at birth is an essential first step in reducing the burden of childhood ALL. Further, this project will be the first of its kind to monitor the persistence of pre-leukemia in early childhood. The proposal is an exceptional opportunity to understand childhood pre-leukemia, is robust in design using three independent studies, and leverages existing NIH investment in pediatric epidemiology. Successful completion of the project will foster epidemiologic innovation including cohort studies of infants at high risk for ALL, allowing us to fill significant gaps in our understanding of the most common childhood cancer. Importantly, the work has the potential to translate into clinical monitoring of ALL in high-risk populations.

抽象的 白血病是最常见的儿童癌症，约占所有癌症诊断的三分之一 在0-14岁的儿童中。有充分的证据表明急性淋巴细胞白血病（全部），最常见 儿童白血病的类型是在子宫内开始的。 ETV6/runx1基因融合，被认为是早期的 在所有后来发展所有人的孩子中，在出生时就出生了所有人的开发活动。孩子们 出生于血细胞中这些白血病特异性易位患有前白血病，并且有必要定义 美食前的流行病学，并确定导致美食前持久性和的因素 向所有人进步。我们已经开发了一种强大的新方法来检测ETV6/runx1前白血病，该方法 使用新生儿血斑。我们建议使用此方法来：1）检查500的新生儿血斑 后来患有白血病的孩子和3000名没有发展白血病的健康儿童以识别 出生前美核血症的决定因素； 2）估计儿童时期的风险均在出生时给予前美洲血症；和 3）评估使用新生儿斑点的童年时期的幼儿园前持续多长时间 儿童的队列，随着时间的流逝，幼儿时期收集的血液样本。这些目标在一起将使我们 确定有多少所有患有白血病基因融合的孩子；哪些因素可以预测前 出生时白血病；有多少从未发展为白血病的孩子出生于基因融合；还有多长时间 基因融合在童年时期一直存在。 建立真正的人口流行率和ETV6/runx1基因融合的决定因素是必不可少的 减轻童年的负担的第一步。此外，该项目将是第一个监视 幼儿时期的美食前的持久性。该提议是一个理解的典型机会 童年时期的leukemia，使用三个独立研究在设计方面非常强大，并利用现有的NIH 小儿流行病学的投资。该项目的成功完成将促进流行病学创新 包括对所有人高风险的婴儿的队列研究 最常见的儿童癌症。重要的是，这项工作有可能转化为临床监测 在高风险人群中。