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.

摘要 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。有强有力的证据表明，急性淋巴细胞白血病（ALL），最常见的 一种儿童白血病，在子宫内就开始了。ETV 6/RUNX 1基因融合，被认为是早期的 ALL发展的起始事件，在一些后来发展为ALL的儿童中存在于出生时。儿童 天生具有这些白血病特异性易位的血细胞是否有白血病前期，有必要进行界定 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。我们开发了一种检测ETV 6/RUNX 1白血病前期的稳健新方法， 使用新生儿的血点我们建议用这种方法：1）检查500例新生儿血斑， 这些儿童后来患上了白血病，3000名健康儿童没有患上白血病， 出生时白血病前期的决定因素; 2）估计出生时白血病前期儿童ALL的风险;以及 3)使用新生儿血斑和相同的血液样本，评估白血病前期在儿童期持续多久。 儿童队列，在幼儿期随时间收集的血液样本。这些目标将使我们能够 确定有多少ALL患儿出生时携带白血病基因融合;哪些因素预测了前 出生时患白血病;有多少从未患白血病的儿童出生时带有基因融合;以及 这种基因融合在儿童时期持续存在。 确定出生时ETV 6/RUNX 1基因融合的真实人群患病率和决定因素是至关重要的， 减轻儿童ALL负担的第一步。此外，该项目将是第一个监测 儿童早期白血病前期的持续存在。这个提议是一个难得的机会， 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 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高危婴儿的队列研究，使我们能够填补我们对 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 在高危人群中。