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The intricate interplay between Clonal Hematopoiesis (CH) and the repercussions of cancer therapies has garnered significant research focus in recent years. Previously perceived as an age-related phenomenon, CH is now closely linked to inflammation ("Inflammaging") and cancer, impacting leukemogenesis, cancer progression, and treatment responses. This review explores the complex interplay between CH and diverse cancer therapies, including chemotherapy, targeted treatments, radiation, stem cell transplants, CAR-T cell therapy, and immunotherapy, like immune checkpoint inhibitors. Notably, knowledge about post-chemotherapy CH mutation/acquisition has evolved from a de novo incident to more of a clonal selection process. Chemotherapy and radiation exposure, whether therapeutic or environmental, increases CH risk, particularly in genes like TP53 and PPM1D. Environmental toxins, especially in high-risk environments like post-disaster sites or space exploration, are associated with CH. CH affects clinical outcomes in stem cell transplant scenarios, including engraftment, survival, and t-MN development. The presence of CH also alters CAR-T cell therapy responses and impacts the efficacy and toxicity of immunotherapies. Furthermore, specific mutations like DNMT3A and TET2 thrive under inflammatory stress, influencing therapy outcomes and justifying the ongoing tailored interventions in clinical trials. This review underscores the critical need to integrate CH analysis into personalized medicine, enhancing risk assessments and refining treatment strategies. As we progress, multidisciplinary collaboration and comprehensive studies are imperative. Understanding CH's impact, especially concerning genotoxic stressors, will inform screening, surveillance, and early detection strategies, decreasing the risk of therapy-related myeloid neoplasms and revolutionizing cancer treatment paradigms. Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.


Abhay Singh, Suresh Balasubramanian. The crossroads of cancer therapies and clonal hematopoiesis. Seminars in hematology. 2024 Feb;61(1):16-21

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PMID: 38403501

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