Clonal Hematopoiesis of Indeterminate Potential as a Novel Risk Factor for Donor-Derived Leukemia

Abstract

Hematopoietic stem cell transplantation (HSCT) is a critical treatment modality for many hematological and non-hematological diseases that is being extended to treat older individuals. However, recent studies show that clonal hematopoiesis of indeterminate potential (CHIP), a common, asymptomatic condition characterized by the expansion of age-acquired somatic mutations in blood cell lineages, may be a risk factor for the development of donor-derived leukemia (DDL), unexplained cytopenias, and chronic graft-versus-host disease. CHIP may contribute to the pathogenesis of these significant transplant complications via various cell-autonomous and non-cell-autonomous mechanisms, and the clinical presentation of DDL may be broader than anticipated. A more comprehensive understanding of the contributions of CHIP to DDL may have important implications for the screening of donors and will improve the safety of HSCT. The objective of this review is to discuss studies linking DDL and CHIP and to explore potential mechanisms by which CHIP may contribute to DDL.