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ResearchIn-Press PreviewClinical ResearchGeneticsOncology Open Access | 10.1172/JCI204429

Evolution of clonal hematopoiesis during cancer treatment and its impact on outcomes

Mona Arabzadeh,1 Yi-Han Tang,2 Christelle Colin-Leitzinger,2 Sadegh Marzban,3 Daniel Walgenbach,4 Stefania Morganti,5 Vaidhyanathan Mahaganapathy,1 Erika Harper,6 Mingxiang Teng,7 Jacob K. Kresovich,2 Iman Washington,8 Heather A. Parsons,5 Judy E. Garber,5 Jeffrey West,3 Shridar Ganesan,1 Hossein Khiabanian,1 and Nancy Gillis2

1Center for Systems and Computational Biology, Rutgers Cancer Institute, Rutgers University, New Brunswick, United States of America

2Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

3Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

4Department of Internal Medicine, University of South Florida, Tampa, United States of America

5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

6Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

7Department of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, United States of America

8Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

Find articles by Arabzadeh, M. in: PubMed | Google Scholar

1Center for Systems and Computational Biology, Rutgers Cancer Institute, Rutgers University, New Brunswick, United States of America

2Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

3Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

4Department of Internal Medicine, University of South Florida, Tampa, United States of America

5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

6Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

7Department of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, United States of America

8Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

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1Center for Systems and Computational Biology, Rutgers Cancer Institute, Rutgers University, New Brunswick, United States of America

2Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

3Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

4Department of Internal Medicine, University of South Florida, Tampa, United States of America

5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

6Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

7Department of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, United States of America

8Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

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1Center for Systems and Computational Biology, Rutgers Cancer Institute, Rutgers University, New Brunswick, United States of America

2Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

3Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

4Department of Internal Medicine, University of South Florida, Tampa, United States of America

5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

6Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

7Department of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, United States of America

8Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

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1Center for Systems and Computational Biology, Rutgers Cancer Institute, Rutgers University, New Brunswick, United States of America

2Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

3Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

4Department of Internal Medicine, University of South Florida, Tampa, United States of America

5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

6Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

7Department of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, United States of America

8Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

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1Center for Systems and Computational Biology, Rutgers Cancer Institute, Rutgers University, New Brunswick, United States of America

2Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

3Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

4Department of Internal Medicine, University of South Florida, Tampa, United States of America

5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

6Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

7Department of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, United States of America

8Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

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1Center for Systems and Computational Biology, Rutgers Cancer Institute, Rutgers University, New Brunswick, United States of America

2Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

3Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

4Department of Internal Medicine, University of South Florida, Tampa, United States of America

5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

6Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

7Department of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, United States of America

8Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

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1Center for Systems and Computational Biology, Rutgers Cancer Institute, Rutgers University, New Brunswick, United States of America

2Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

3Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

4Department of Internal Medicine, University of South Florida, Tampa, United States of America

5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

6Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

7Department of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, United States of America

8Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

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1Center for Systems and Computational Biology, Rutgers Cancer Institute, Rutgers University, New Brunswick, United States of America

2Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

3Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

4Department of Internal Medicine, University of South Florida, Tampa, United States of America

5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

6Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

7Department of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, United States of America

8Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

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1Center for Systems and Computational Biology, Rutgers Cancer Institute, Rutgers University, New Brunswick, United States of America

2Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

3Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

4Department of Internal Medicine, University of South Florida, Tampa, United States of America

5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

6Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

7Department of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, United States of America

8Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

Find articles by Kresovich, J. in: PubMed | Google Scholar

1Center for Systems and Computational Biology, Rutgers Cancer Institute, Rutgers University, New Brunswick, United States of America

2Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

3Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

4Department of Internal Medicine, University of South Florida, Tampa, United States of America

5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

6Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

7Department of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, United States of America

8Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

Find articles by Washington, I. in: PubMed | Google Scholar

1Center for Systems and Computational Biology, Rutgers Cancer Institute, Rutgers University, New Brunswick, United States of America

2Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

3Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

4Department of Internal Medicine, University of South Florida, Tampa, United States of America

5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

6Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

7Department of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, United States of America

8Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

Find articles by Parsons, H. in: PubMed | Google Scholar

1Center for Systems and Computational Biology, Rutgers Cancer Institute, Rutgers University, New Brunswick, United States of America

2Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

3Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

4Department of Internal Medicine, University of South Florida, Tampa, United States of America

5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

6Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

7Department of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, United States of America

8Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

Find articles by Garber, J. in: PubMed | Google Scholar |

1Center for Systems and Computational Biology, Rutgers Cancer Institute, Rutgers University, New Brunswick, United States of America

2Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

3Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

4Department of Internal Medicine, University of South Florida, Tampa, United States of America

5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

6Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

7Department of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, United States of America

8Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

Find articles by West, J. in: PubMed | Google Scholar

1Center for Systems and Computational Biology, Rutgers Cancer Institute, Rutgers University, New Brunswick, United States of America

2Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

3Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

4Department of Internal Medicine, University of South Florida, Tampa, United States of America

5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

6Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

7Department of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, United States of America

8Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

Find articles by Ganesan, S. in: PubMed | Google Scholar

1Center for Systems and Computational Biology, Rutgers Cancer Institute, Rutgers University, New Brunswick, United States of America

2Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

3Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

4Department of Internal Medicine, University of South Florida, Tampa, United States of America

5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

6Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

7Department of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, United States of America

8Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

Find articles by Khiabanian, H. in: PubMed | Google Scholar

1Center for Systems and Computational Biology, Rutgers Cancer Institute, Rutgers University, New Brunswick, United States of America

2Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

3Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

4Department of Internal Medicine, University of South Florida, Tampa, United States of America

5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

6Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

7Department of Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, United States of America

8Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, United States of America

Find articles by Gillis, N. in: PubMed | Google Scholar

Published June 9, 2026 - More info

J Clin Invest. https://doi.org/10.1172/JCI204429.
Copyright © 2026, Arabzadeh et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published June 9, 2026 - Version history
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Abstract

Clonal hematopoiesis (CH) is the age-related expansion of mutated hematopoietic stem cells without hematologic abnormalities. In patients with solid tumors, CH is associated with higher mortality and may evolve to therapy-related myeloid neoplasms; however, the mechanisms by which cancer treatments promote CH dynamics remain largely unknown. Here, we analyzed 392 serial samples from a prospective cohort of breast cancer patients and showed that cytotoxic treatments led to strong therapeutic bottlenecks, resulting in significant reductions in hematopoietic allelic populations and differential clonal selection. Positively selected CH that expanded through dose-dependent therapeutic bottlenecks harbored mutations in TP53, PPM1D, SRCAP, DNMT3A, and YLPM1. Patients with positively selected CH during treatment had the shortest progression-free and overall survival compared to patients with unchanging or negatively selected CH across all therapies. These findings, validated in independent breast cancer and pan-cancer cohorts, provide strong evidence for clinical relevance of monitoring CH during cancer treatment.

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  • Version 1 (June 9, 2026): In-Press Preview
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