The vicious and virtuous circles of clonal hematopoiesis: Clonal hematopoiesis can exist as both a driver and a consequence of inflammatory dysregulation.

The expansion of hematopoietic stem/progenitor cells (HSPCs) with specific, recurrent genetic variants in people without a diagnosis of hematological malignancy is called ‘clonal hematopoiesis’ (CH)1. CH is composed of many diverse entities and can be subcategorized according to the specific gene involved, the mutation subtype, the etiology, and related clinical features, including age, blood-count effects and associated comorbidities. The mutational subtypes of CH are defined by the presence of single-nucleotide variants and small insertions and/or deletions, or large-scale mosaic chromosomal alterations (mCAs), and its etiology can be infectious, genotoxic, autoimmune or metabolic, with each providing distinct fitness advantages to clones. Two articles published in this issue of Nature Medicine link novel etiological and context-specific clinical features to CH. Dharan et al. present chronic infection with human immunodeficiency virus (HIV) as a novel etiology for CH, characterized by specific gene associations and clonal dynamics2, whereas Zekavat et al. demonstrate the association of mCAs with a wide range of infections, including infection with the coronavirus SARS-CoV-23. Key to the connection between these manuscripts is the self-perpetuating circle of inflammation and clonal expansion.