Clonal hematopoiesis in sickle cell disease.

Autor: Liggett LA; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA., Cato LD; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA., Weinstock JS; Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA., Zhang Y; Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Nouraie SM; Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Gladwin MT; Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Garrett ME; Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA., Ashley-Koch A; Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA., Telen MJ; Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA., Custer B; Vitalant Research Institute, San Francisco, California, USA.; Department of Laboratory Medicine, UCSF, San Francisco, California, USA., Kelly S; Vitalant Research Institute, San Francisco, California, USA.; Division of Pediatric Hematology, UCSF Benioff Children's Hospital, Oakland, California, USA., Dinardo CL; Fundação Pró-Sangue Hemocentro de São Paulo, São Paulo, Brazil.; Institute of Tropical Medicine, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil., Sabino EC; Institute of Tropical Medicine, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil., Loureiro P; Fundação Hemope, Recife, Pernambuco, Brazil., Carneiro-Proietti AB; Fundação Hemominas, Belo Horizonte, Brazil., Maximo C; Fundação Hemorio, Rio de Janeiro, Brazil., Reiner AP; Department of Epidemiology, University of Washington, Seattle, Washington, USA.; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA., Abecasis GR; Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA., Williams DA; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA., Natarajan P; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Bick AG; Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Sankaran VG; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.; Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.
Jazyk: angličtina
Zdroj: The Journal of clinical investigation [J Clin Invest] 2022 Feb 15; Vol. 132 (4).
DOI: 10.1172/JCI156060
Abstrakt: BACKGROUNDCurative gene therapies for sickle cell disease (SCD) are currently undergoing clinical evaluation. The occurrence of myeloid malignancies 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 premalignant 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, limited data addressing this issue have been reported.METHODSHere, we leveraged 74,190 whole-genome sequences to robustly study CH in SCD. Somatic mutation calling methods were used to assess CH in all samples and comparisons between individuals with and without SCD were performed.RESULTSWhile we had sufficient power to detect a greater than 2-fold increased rate of CH, we found no detectable variation in rate or clone properties between individuals affected by SCD and controls. The rate of CH in individuals with SCD was unaltered by hydroxyurea use.CONCLUSIONSWe did not observe an increased risk for acquiring detectable CH in SCD, at least as measured by whole-genome sequencing. These results should help guide ongoing efforts and further studies 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.FUNDINGNew York Stem Cell Foundation and the NIH.
Databáze: MEDLINE