Increased prevalence of clonal hematopoiesis in children with sickle cell disease
Abstract
Abstract Recent studies have reached opposing conclusions about whether clonal hematopoiesis (CH) is increased or decreased in patients with sickle cell disease (SCD). Given that CH is typically age-related, its presence in children with SCD could offer unique insights into early-life mutagenesis and disease-related stressors. We tested the primary and secondary hypotheses that children with SCD would have a higher prevalence of CH than age-, sex-, and race-matched children without SCD and that children with hydroxyurea would have a higher CH prevalence than children not treated with hydroxyurea. To address this, we conducted a cross-sectional study in 2 independent cohorts of children aged 0 to 18 years with SCD (N = 1025 and N = 1293, respectively) and a 2957-person matched comparison group. Using a highly sensitive, error-corrected sequencing assay capable of detecting CH at a variant allele frequency of ≥0.5%, we found that children with SCD have a significantly higher prevalence of CH than the comparison group (odds ratio [OR], 4.2; P = 7.4 × 10−13). In addition, CH was not associated with exposure to hydroxyurea therapy (OR, 0.76; P = .44).
Article Details
Authors (15)
Jessica Ulloa
1Human Genetics Program, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN
Kristin Wuichet
2Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
Sara R. Rashkin
3Department of Hematology, St. Jude Children’s Research Hospital, Memphis, TN
Yash Pershad
Connor Shore
2Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
Caitlyn Vlasschaert
4Department of Medicine, Queen’s University, Kingston, ON, Canada
Mark Rodeghier
5Rodeghier Consulting, Chicago, IL
Yu Yao
Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Institute of Fine Chemicals, School of Chemistry and Molecular Engineering
Victor R. Gordeuk
Binal N. Shah
6Division of Hematology and Oncology, University of Illinois Chicago, Chicago, IL
Clifford M. Takemoto
3Department of Hematology, St. Jude Children’s Research Hospital, Memphis, TN
Santosh L. Saraf
1Comprehensive Sickle Cell Center, Division of Hematology and Oncology, Department of Medicine, University of Illinois Chicago, Chicago, IL
Michael R. DeBaun
7Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN
Mitchell J. Weiss
Alexander G. Bick