title: Identifying Inherited and Acquired Genetic Factors Involved in Poor Stem Cell Mobilization and Donor-Derived Malignancy.
abstract: Analysis of the clinical characteristics of hematopoietic stem cell transplant (HSCT) donors has proven beneficial for identifying cases of heritable hematopoietic disorders. This study examines poor peripheral blood hematopoietic stem cell mobilization after granulocyte colony-stimulating factor administration among 328 donors as a potential marker for suspected familial predisposition to myeloid malignancies. Here, we present data comparing the clinical characteristics of poor-mobilizing versus nonpoor-mobilizing donors and the results of panel-based sequencing of hematopoietic genes in poor-mobilizing donors. From this analysis, we identified a novel case of a donor-derived myelodysplastic syndrome in an HSCT recipient that is consistent with clonal evolution of TET2-mutated clonal hematopoiesis of indeterminate potential (CHIP) within the donor. This study demonstrates the potential risk of using hematopoietic stem cells from a donor with CHIP and raises the question of whether there should be increased screening measures to identify such donors.
authors: Section of Hematology/Oncology, Department of Medicine, and The University of Chicago Comprehensive Cancer Center, The University of Chicago, Chicago, Illinois.
authors: Katarzyna
authors: K
authors: Rojek
authors: Section of Hematology/Oncology, Department of Medicine, and The University of Chicago Comprehensive Cancer Center, The University of Chicago, Chicago, Illinois.
authors: Eric
authors: E
authors: Nickels
authors: Section of Hematology/Oncology, Department of Medicine, and The University of Chicago Comprehensive Cancer Center, The University of Chicago, Chicago, Illinois.
authors: Barbara
authors: B
authors: Neistadt
authors: Section of Hematology/Oncology, Department of Medicine, and The University of Chicago Comprehensive Cancer Center, The University of Chicago, Chicago, Illinois.
authors: Rafael
authors: R
authors: Marquez
authors: Section of Hematology/Oncology, Department of Medicine, and The University of Chicago Comprehensive Cancer Center, The University of Chicago, Chicago, Illinois.
authors: Amittha
authors: A
authors: Wickrema
authors: Section of Hematology/Oncology, Department of Medicine, and The University of Chicago Comprehensive Cancer Center, The University of Chicago, Chicago, Illinois.
authors: Andrew
authors: A
authors: Artz
authors: Section of Hematology/Oncology, Department of Medicine, and The University of Chicago Comprehensive Cancer Center, The University of Chicago, Chicago, Illinois.
authors: Koen
authors: K
authors: van Besien
authors: Section of Hematology/Oncology, Department of Medicine, and The University of Chicago Comprehensive Cancer Center, The University of Chicago, Chicago, Illinois.
authors: Richard A
authors: RA
authors: Larson
authors: Department of Medicine, Division of Medical Genetics, and Department of Genome Sciences, University of Washington, Seattle, Washington.
authors: Ming K
authors: MK
authors: Lee
authors: Division of Genomic and Molecular Pathology, Department of Pathology, University of Chicago, Chicago, Illinois.
authors: Jeremy P
authors: JP
authors: Segal
authors: Department of Medicine, Division of Medical Genetics, and Department of Genome Sciences, University of Washington, Seattle, Washington.
authors: Mary-Claire
authors: MC
authors: King
authors: Department of Medicine, Division of Medical Genetics, and Department of Genome Sciences, University of Washington, Seattle, Washington.
authors: Tom
authors: T
authors: Walsh
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Pediatric Hematology/Oncology, Seattle Children's Hospital, and Department of Pediatrics, University of Washington, Seattle, Washington.
authors: Akiko
authors: A
authors: Shimamura
authors: Department of Medicine, Division of Hematology, University of Washington, Seattle, Washington.
authors: Sioban B
authors: SB
authors: Keel
authors: Section of Hematology/Oncology, Department of Medicine, and The University of Chicago Comprehensive Cancer Center, The University of Chicago, Chicago, Illinois; Center for Clinical Cancer Genetics, The University of Chicago, Chicago, Illinois.
authors: Jane E
authors: JE
authors: Churpek
authors: Section of Hematology/Oncology, Department of Medicine, and The University of Chicago Comprehensive Cancer Center, The University of Chicago, Chicago, Illinois; Center for Clinical Cancer Genetics, The University of Chicago, Chicago, Illinois. Electronic address: lgodley@medicine.bsd.uchicago.edu.
authors: Lucy A
authors: LA
authors: Godley
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001782:Blood Donors; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D049308:Dioxygenases; D005260:Female; D020022:Genetic Predisposition to Disease; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006410:Hematopoiesis / Q000235:genetics; D019650:Hematopoietic Stem Cell Mobilization / Q000592:standards*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics; D009369:Neoplasms / Q000209:etiology / Q000235:genetics*; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016179:Granulocyte Colony-Stimulating Factor; D049308:Dioxygenases; C541081:TET2 protein, human
keywords: Clonal hematopoiesis of indeterminate potential; Donor-derived leukemia; TET2 mutation