Clonal hematopoiesis: Mutation-specific adaptation to environmental change

Marcus A Florez; Brandon T Tran; Trisha K Wathan; James DeGregori; Eric M Pietras; Katherine Y King

doi:10.1016/j.stem.2022.05.006

Clonal hematopoiesis: Mutation-specific adaptation to environmental change

Cell Stem Cell. 2022 Jun 2;29(6):882-904. doi: 10.1016/j.stem.2022.05.006.

Authors

Marcus A Florez¹, Brandon T Tran², Trisha K Wathan³, James DeGregori⁴, Eric M Pietras⁵, Katherine Y King⁶

Affiliations

¹ Medical Scientist Training Program and Program in Translational Biology and Molecular Medicine, Graduate School of Biomedical Sciences, Baylor College of Medicine, 1102 Bates Street, Suite 1150, Houston, TX 77030, USA; Division of Infectious Disease, Department of Pediatrics, Baylor College of Medicine, 1102 Bates Street, Suite 1150, Houston, TX 77030, USA.
² Graduate School of Biomedical Sciences, Program in Cancer and Cell Biology, Baylor College of Medicine, 1102 Bates Street, Suite 1150, Houston, TX 77030, USA; Division of Infectious Disease, Department of Pediatrics, Baylor College of Medicine, 1102 Bates Street, Suite 1150, Houston, TX 77030, USA.
³ Division of Infectious Disease, Department of Pediatrics, Baylor College of Medicine, 1102 Bates Street, Suite 1150, Houston, TX 77030, USA.
⁴ Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Division of Hematology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Microbiology and Immunology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁵ Division of Hematology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Microbiology and Immunology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁶ Medical Scientist Training Program and Program in Translational Biology and Molecular Medicine, Graduate School of Biomedical Sciences, Baylor College of Medicine, 1102 Bates Street, Suite 1150, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, Program in Cancer and Cell Biology, Baylor College of Medicine, 1102 Bates Street, Suite 1150, Houston, TX 77030, USA; Division of Infectious Disease, Department of Pediatrics, Baylor College of Medicine, 1102 Bates Street, Suite 1150, Houston, TX 77030, USA; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, 1102 Bates Street, Suite 1150, Houston, TX 77030, USA. Electronic address: [email protected].

Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) describes a widespread expansion of genetically variant hematopoietic cells that increases exponentially with age and is associated with increased risks of cancers, cardiovascular disease, and other maladies. Here, we discuss how environmental contexts associated with CHIP, such as old age, infections, chemotherapy, or cigarette smoking, alter tissue microenvironments to facilitate the selection and expansion of specific CHIP mutant clones. Further, we consider major remaining gaps in knowledge, including intrinsic effects, clone size thresholds, and factors affecting clonal competition, that will determine future application of this field in transplant and preventive medicine.

Keywords: aging; cancer; chemotherapy; clonal competition; clonal hematopoiesis; infection; inflammation; radiation.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Clonal Hematopoiesis* / genetics
Hematopoiesis / genetics
Hematopoietic Stem Cells*
Mutation / genetics
Risk Factors

Abstract

Publication types

MeSH terms

Grants and funding