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Grant Details

Grant Number: 5R01CA269393-02 Interpret this number
Primary Investigator: Marcotte, Erin
Organization: University Of Minnesota
Project Title: Prevalence and Persistence of the Etv6/Runx1 Pre-Leukemic Clone
Fiscal Year: 2024


Abstract

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.



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