Distinct Landscape and Clinical Implications of Therapy-Related Clonal Hematopoiesis

Authors

Koichi Takahashi
Daisuke Nakada
Margaret Goodell

Publication Date

10-1-2024

Journal

The Journal of Clinical Investigation

Abstract

Therapy-related clonal hematopoiesis (t-CH) is defined as clonal hematopoiesis detected in individuals previously treated with chemotherapy and/or radiation therapy. With the increased use of genetic analysis in oncological care, the detection of t-CH among cancer patients is becoming increasingly common. t-CH arises through the selective bottleneck imposed by chemotherapies and potentially through direct mutagenesis from chemotherapies, resulting in a distinct mutational landscape enriched with mutations in DNA damage-response pathway genes such as TP53, PPM1D, and CHEK2. Emerging evidence sheds light on the mechanisms of t-CH development and potential strategies to mitigate its emergence. Due to its unique characteristics that predominantly affect cancer patients, t-CH has clinical implications distinct from those of CH in the general population. This Review discusses the potential mechanisms of t-CH development, its mutational landscape, mutant-drug relationships, and its clinical significance. We highlight the distinct nature of t-CH and call for intensified research in this field.

Keywords

Humans, Clonal Hematopoiesis, Mutation, Neoplasms, Checkpoint Kinase 2, Protein Phosphatase 2C, Tumor Suppressor Protein p53, Neoplasm Proteins

Comments

PMID: 39352380

DOI

10.1172/JCI180069

PMID

39352380

PMCID

PMC11444158

PubMedCentral® Posted Date

October 2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes