Clonal hematopoiesis in sickle cell disease
Clonal hematopoiesis in sickle cell disease
Abstract Curative gene therapies for sickle cell disease (SCD) are currently undergoing clinical evaluation. However, the occurrence of several myeloid malignancy cases in these trials has prompted safety concerns. Individuals with SCD are predisposed to myeloid malignancies, but the underlying causes remain undefined. Clonal hematopoiesis (CH) is a pre-malignant condition that also confers significant predisposition to myeloid cancers. While it has been speculated that CH may play a role in SCD-associated cancer predisposition, no data addressing this issue have been reported. Here, we leverage 74,190 whole-genome sequences to robustly study CH in SCD. While we have sufficient power to detect increased rates of CH, we find no variation in rate or clone properties between individuals affected by SCD and controls. These results should help guide ongoing efforts that seek to better define the risk factors underlying myeloid malignancy predisposition in SCD and help ensure that curative therapies can be more safely applied.
Loureiro Paula、Reiner Alexander P.、Weinstock Joshua S.、Nouraie Seyed Mehdi、Gladwin Mark T.、Ashley-Koch Allison、Custer Brian、Kelly Shannon、NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium、Cato Liam D.、Williams David A.、Telen Marilyn J.、Bick Alexander G.、Sankaran Vijay G.、Liggett L. Alexander、Natarajan Pradeep、Zhang Yingze、Maximo Cl¨￠udia、Carneiro-Proietti Anna B¨￠rbara、Garrett Melanie E.、Sabino Ester C.、Abecasis Gon?alo R.、Dinardo Carla Luana
Pernambuco State Center of Hematology and HemotherapyDepartment of Epidemiology, University of Washington||Division of Public Health Sciences, Fred Hutchinson Cancer Research CenterCenter for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public HealthDepartment of Medicine, School of Medicine, University of PittsburghDepartment of Medicine, School of Medicine, University of PittsburghDepartment of Medicine, Duke University Medical CenterVitalant Research Institute||Department of Laboratory Medicine, University of CaliforniaVitalant Research Institute||Division of Pediatric Hematology, UCSF Benioff Children?ˉs HospitalDivision of Hematology/Oncology, Boston Children?ˉs Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School||Broad Institute of MIT and HarvardDivision of Hematology/Oncology, Boston Children?ˉs Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical SchoolDivision of Hematology/Oncology, Boston Children?ˉs Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School||Department of Medicine, Duke University Medical CenterDivision of Genetic Medicine, Department of Medicine, Vanderbilt University Medical CenterDivision of Hematology/Oncology, Boston Children?ˉs Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School||Broad Institute of MIT and Harvard||Harvard Stem Cell InstituteDivision of Hematology/Oncology, Boston Children?ˉs Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School||Broad Institute of MIT and HarvardBroad Institute of MIT and Harvard||Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Medicine, School of Medicine, University of PittsburghFunda??o HemorioFunda??o HemominasDepartment of Medicine, Duke University Medical CenterInstitute of Tropical Medicine, Faculdade de Medicina da Universidade de S?o PauloCenter for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public HealthFunda??o Pr¨?-Sangue Hemocentro de S?o Paulo||Institute of Tropical Medicine, Faculdade de Medicina da Universidade de S?o Paulo
医药卫生理论医学研究方法肿瘤学
Loureiro Paula,Reiner Alexander P.,Weinstock Joshua S.,Nouraie Seyed Mehdi,Gladwin Mark T.,Ashley-Koch Allison,Custer Brian,Kelly Shannon,NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium,Cato Liam D.,Williams David A.,Telen Marilyn J.,Bick Alexander G.,Sankaran Vijay G.,Liggett L. Alexander,Natarajan Pradeep,Zhang Yingze,Maximo Cl¨￠udia,Carneiro-Proietti Anna B¨￠rbara,Garrett Melanie E.,Sabino Ester C.,Abecasis Gon?alo R.,Dinardo Carla Luana.Clonal hematopoiesis in sickle cell disease[EB/OL].(2025-03-28)[2025-08-02].https://www.medrxiv.org/content/10.1101/2021.06.12.21258772.点此复制
评论