Skip to content
DraconiticResearch
Search Sources API
181,716 studies31 sourcesUpdated 28 min ago
Peer-reviewedCC BY 4.0Leukemia

TP53-mutant CHIP defines a pro-inflammatory phenotype and predicts adverse outcomes after CAR T-cell therapy

  • Giulia Rappa1,2,3
  • Frank Ziemann1,3,4,5,6
  • Kieron White1,2
  • Linus Kruk1,7
  • Samar Shamas1,7
  • Amelie Muth1,2
  • Kayleen Shi1,7
  • Cristina Zucchinetti1,2
  • Savanna Süß1,2
  • Maja Rothenberg-Thurley5
  • Alessandra Holzem1
  • Tobias Tix1,7
8 more authors
  • Agnese Petrera8
  • Bianka Ksienzyk5
  • Charlotte Bentenrieder5
  • Katharina S. Götze3,6,9
  • Fabian Müller10
  • Veit Bücklein1,2,3,5,6
  • Kai Rejeski1,3,6,7
  • Marion Subklewe1,2,3,5,6
10 affiliations
  1. 1Department of Medicine III, University Hospital, LMU Munich, Munich, Germany
  2. 2Laboratory for Translational Cancer Immunology, LMU Gene Center, Munich, Germany
  3. 3The Bavarian Cancer Research Center (BZKF), Munich, Germany
  4. 4Experimental Leukemia and Lymphoma Research (ELLF), LMU Munich, Munich, Germany
  5. 5Laboratory for Leukemia Diagnostics (LFL), LMU Munich, Munich, Germany
  6. 6German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany
  7. 7Laboratory for Precision Immunotherapy, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany
  8. 8Metabolomics and Proteomics Core Facility, Helmholtz Zentrum Munich—German Research Center for Environmental Health, Munich, Germany
  9. 9Department of Medicine III, Klinikum Rechts der Isar, Technical University of Munich (TUM) Hospital, Munich, Germany
  10. 10Department of Internal Medicine 5-Hematology and Oncology, University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
Read full textPDFDOICite

Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) has been well-characterized in patients receiving chemotherapy and hematopoietic cell transplantation. However, its immunologic relevance and potential role in modulating chimeric antigen receptor T-cell (CAR-T) therapy-related toxicities, inflammation, and clinical outcomes remains incompletely defined. In this exploratory study of 104 CAR-T recipients, we investigated the prognostic impact of pre-existing CHIP clones on toxicity and survival, and examined CHIP-associated inflammatory proteomic signatures leveraging longitudinal serum samples. Overall CHIP status was not associated with inflammatory toxicities, outcomes, or systemic inflammatory profiles. Analysis of clonal dynamics revealed TP53- and ASXL1-mutated clones to be the dominant expanding CHIP clones post-infusion, whereas DNMT3A- and PPM1D-mutated clones showed reduced clonal abundance over time. Notably, TP53-mutated CHIP was linked to lower platelet and hemoglobin levels, a higher baseline CAR-HEMATOTOX score, inferior clinical outcomes, and a distinct inflammatory signature. These findings identify TP53-mutated CHIP in CAR-T-treated patients as a high-risk CHIP genotype compared with other CHIP mutations. Importantly, patients who developed treatment-emergent myeloid neoplasms after CAR T-cell therapy exhibited distinct patterns of clonal expansion and inflammatory profiles. Together, these findings support a risk-adapted approach prioritizing longitudinal monitoring of TP53-mutated CHIP, especially in patients with high CAR-HEMATOTOX scores who develop cytopenias.

Related

  1. Adverse Graft Remodeling Reflects Dynamic Allograft Stress and Predicts Adverse Outcomes After Heart Transplantation
    K. Patel, T. Pan, S. Al-Kindi +6
    medRxivPreprintAll rights reservedFull textSurgery & anaesthesiamedRxiv
  2. A biomarker risk score predicts adverse cardiovascular outcomes in patients with angina and non-obstructive coronary artery disease
    Jingwen Huang, Ana Leon, Julia Ossi +16
    American journal of preventive cardiologyPeer-reviewedCC BYFull textGeneral medicineEurope PMC
  3. Immune Network Dysregulation Predicts Adverse Outcomes in Infective Endocarditis.
    Isabela Galizzi Fae, Pedro Henrique Oliveira Murta Pinto, Gustavo Brandão Oliveira +9
    Tropical medicine and infectious diseasePeer-reviewedCC BYFull textEpidemiology & public healthEurope PMC
  4. Remnant cholesterol inflammation index predicts adverse outcomes in patients with acute myocardial infarction: a single-center retrospective study
    Xinyue Chen, Yichen Li, Jianwei Ma +7
    Frontiers in Cardiovascular MedicinePeer-reviewedCC BY 4.0Cardiovascular medicineCrossref
  5. MCT1 activity defines an aggressive metabolic phenotype and therapeutic target in non-small cell lung cancer
    R. B. Cameron, K. E. Shema, N. Dubois +14
    bioRxivPreprintCC BYFull textOncologybioRxiv

Cite

BibTeXRIS
BibTeX
@article{rappa2026tp53mutant,
  title = {{TP53-mutant CHIP defines a pro-inflammatory phenotype and predicts adverse outcomes after CAR T-cell therapy}},
  author = {Giulia Rappa and Frank Ziemann and Kieron White and Linus Kruk and Samar Shamas and Amelie Muth and Kayleen Shi and Cristina Zucchinetti and Savanna Süß and Maja Rothenberg-Thurley and Alessandra Holzem and Tobias Tix and Agnese Petrera and Bianka Ksienzyk and Charlotte Bentenrieder and Katharina S. Götze and Fabian Müller and Veit Bücklein and Kai Rejeski and Marion Subklewe},
  journal = {Leukemia},
  year = {2026},
  month = aug,
  doi = {10.1038/s41375-026-03083-1},
  url = {https://doi.org/10.1038/s41375-026-03083-1},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - TP53-mutant CHIP defines a pro-inflammatory phenotype and predicts adverse outcomes after CAR T-cell therapy
AU  - Giulia Rappa
AU  - Frank Ziemann
AU  - Kieron White
AU  - Linus Kruk
AU  - Samar Shamas
AU  - Amelie Muth
AU  - Kayleen Shi
AU  - Cristina Zucchinetti
AU  - Savanna Süß
AU  - Maja Rothenberg-Thurley
AU  - Alessandra Holzem
AU  - Tobias Tix
AU  - Agnese Petrera
AU  - Bianka Ksienzyk
AU  - Charlotte Bentenrieder
AU  - Katharina S. Götze
AU  - Fabian Müller
AU  - Veit Bücklein
AU  - Kai Rejeski
AU  - Marion Subklewe
PY  - 2026
DA  - 2026/08/24
JO  - Leukemia
DO  - 10.1038/s41375-026-03083-1
UR  - https://doi.org/10.1038/s41375-026-03083-1
AB  - Clonal hematopoiesis of indeterminate potential (CHIP) has been well-characterized in patients receiving chemotherapy and hematopoietic cell transplantation. However, its immunologic relevance and potential role in modulating chimeric antigen receptor T-cell (CAR-T) therapy-related toxicities, inflammation, and clinical outcomes remains incompletely defined. In this exploratory study of 104 CAR-T recipients, we investigated the prognostic impact of pre-existing CHIP clones on toxicity and survival, and examined CHIP-associated inflammatory proteomic signatures leveraging longitudinal serum samples. Overall CHIP status was not associated with inflammatory toxicities, outcomes, or systemic inflammatory profiles. Analysis of clonal dynamics revealed TP53- and ASXL1-mutated clones to be the dominant expanding CHIP clones post-infusion, whereas DNMT3A- and PPM1D-mutated clones showed reduced clonal abundance over time. Notably, TP53-mutated CHIP was linked to lower platelet and hemoglobin levels, a higher baseline CAR-HEMATOTOX score, inferior clinical outcomes, and a distinct inflammatory signature. These findings identify TP53-mutated CHIP in CAR-T-treated patients as a high-risk CHIP genotype compared with other CHIP mutations. Importantly, patients who developed treatment-emergent myeloid neoplasms after CAR T-cell therapy exhibited distinct patterns of clonal expansion and inflammatory profiles. Together, these findings support a risk-adapted approach prioritizing longitudinal monitoring of TP53-mutated CHIP, especially in patients with high CAR-HEMATOTOX scores who develop cytopenias.
SN  - 0887-6924
SN  - 1476-5551
ER  -