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 0-14岁儿童。有强有力的证据表明，急性淋巴细胞白血病（ALL）是最常见的 儿童白血病的一种类型，是在子宫内开始的。 ETV6/RUNX1基因融合，被认为是早期的 ALL 发展的始动事件在一些后来发展为 ALL 的儿童中出生时就存在。孩子们 出生时患有这些白血病特异性血细胞易位的人患有白血病前期，因此需要定义 白血病前期的流行病学并确定导致白血病前期持续存在的因素 进展为 ALL。我们开发了一种强大的新方法来检测 ETV6/RUNX1 白血病前期， 使用新生儿血斑。我们建议使用该方法： 1）检查500个新生儿血斑 后来患上白血病的儿童和 3000 名未患上白血病的健康儿童进行了鉴定 出生时白血病前期的决定因素； 2) 估计出生时接受白血病前期治疗的儿童 ALL 的风险；和 3) 使用新生儿血斑评估白血病前期在儿童期持续多久 儿童队列，在幼儿时期随时间收集的血液样本。这些目标共同将使我们能够 确定有多少患有 ALL 的儿童出生时就带有白血病基因融合；哪些因素可以预测预 出生时患有白血病；有多少从未患上白血病的儿童出生时就带有基因融合；以及多长时间 基因融合在童年时期持续存在。 确定出生时 ETV6/RUNX1 基因融合的真实人群患病率和决定因素至关重要 减轻儿童ALL负担的第一步。此外，该项目将是同类项目中第一个监测 儿童早期白血病前期的持续存在。该提案是了解的绝佳机会 儿童白血病前期，使用三项独立研究设计稳健，并利用现有的 NIH 对儿科流行病学的投资。该项目的成功完成将促进流行病学创新 包括对 ALL 高危婴儿进行的队列研究，使我们能够填补我们对以下疾病理解的重大空白： 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 高危人群中 ALL 的发生率。