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Determinants of Myeloid Clonal Evolution

骨髓克隆进化的决定因素

基本信息

批准号：
10591686
负责人：
Kristen E Schratz
金额：
$ 17.17万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-01-05 至 2027-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10591686
关键词：
Adult Affect African American Age Aging Applications Grants Automobile Driving Baltimore Biological Markers Blood Chromosomes Clinical Clonal Evolution Clonality Communities Computational Biology DNA Damage Data Development Disease Disease Outcome Disease Progression Dysmyelopoietic Syndromes Early identification Environment Erythrocytes Etiology Event Gene Mutation Genes Genetic Germ-Line Mutation Goals Hematologic Neoplasms Hematological Disease Hematopoiesis Hematopoietic Heritability Individual Inherited JAK2 gene Knowledge Lead Length Life Link Longterm Follow-up Malignant Neoplasms Measures Mendelian disorder Mentors Mentorship Mutation Myelodysplastic/Myeloproliferative Disease Myelogenous Myeloproliferative disease Participant Patients Pattern Phenotype Phylogenetic Analysis Polycythemia Vera Population Population Control Prevalence Prevention Production Publications RNA-Directed DNA Polymerase Reporting Risk Risk Factors Role Sampling Solid Syndrome Telomerase Telomerase RNA Component Testing Training United States Universities Untranslated RNA Woman Women&apos s Health Work age related autosome biobank cohort disorder risk gain of function mutation genetic epidemiology leukemia loss of function loss of function mutation medical schools mutant novel novel marker novel strategies population based predictive marker premature promoter reconstruction response sequencing platform skills specific biomarkers stem cells telomere trait

项目摘要

PROJECT ABSTRACT Clonal hematopoiesis is acquired with aging, and in some cases, precedes the onset of both myelodysplastic and myeloproliferative disorders. However, the genetic drivers that underlie the evolution of clonal hematopoiesis and the subsequent disease risk remain poorly understood. This proposal builds on generated evidence showing that telomere length, a genetic and clinically available biomarker, predisposes to clonal hematopoiesis in Mendelian syndromes. We have also found evidence for distinct clonal hematopoiesis mutations that appear to differentially predispose to hypoplastic and myeloproliferative phenotypes. In this application, we will examine the role of telomere length in driving clonal evolution with aging in well- characterized cohorts including a Baltimore-based cohort of community-based women with a large African American subset. Additionally, we will also examine the onset and prevalence of a novel clonal hematopoiesis mutation in the telomerase reverse transcriptase gene that appears to be protective against myeloid malignancies. This K08 grant application is supported by outstanding mentors and in a strong translational environment at Johns Hopkins University School of Medicine with a detailed mentorship and training plan that focuses on genetic epidemiology and computational biology skills. The knowledge has the potential to impact current paradigms related to hematopoietic aging, myeloid clonal disease risk as well as novel biomarkers of specific disease risk and progression.

项目摘要