ArticleThe Journal of clinical investigation2026
Mutant p53 promotes clonal hematopoiesis by generating a chronic inflammatory microenvironment.
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Article in The Journal of clinical investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Chemotherapy-induced thrombocytopenia: from "platelet counting" to ecological repair of the bone marrow.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Review
- TP53-mutant CHIP defines a pro-inflammatory phenotype and predicts adverse outcomes after CAR T-cell therapy.Leukemia · 2026Article
- Inflammatory Signatures in MDS: The Missing Link Between Genetics, Microenvironment, and Therapy.Cells · 2026Review
- Immune responses in aging adults.The Journal of clinical investigation · 2026Review
- G protein-coupled receptor 56-mediated lung metastasis mechanisms in osteosarcoma LM8 cells.Medical molecular morphology · 2026Article
- Therapeutic potential of targeting macrophage polarization in metastatic gastric cancer: a review on core mechanisms and clinical progress.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Targeting ZNF570 activates ferroptosis to reverse tamoxifen resistance in ER + breast cancer cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Transferosomes as Advanced Nanocarriers for Enhanced Drug Delivery in Skin Cancer Therapy: A Comprehensive Review.Applied biochemistry and biotechnology · 2026Review
- Targeting STAT3 by SH-4-54 suppresses the occurrence and inactivates oxidative phosphorylation in small-cell lung cancer via the SRC signaling.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Beyond survival: psychoneuroimmunology-driven cancer psychological rehabilitation-a paradigm shift from symptom management to biobehavioral remodeling.Frontiers in oncology · 2026Review
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Authors and funding
51 authors.
Sisi ChenPrecision Research Center for Refractory Diseases, Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Sergio BarajasDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Sasidhar VemulaDepartment of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Yuxia YangDepartment of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Ed SimpsonDepartment of Medical Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Hongyu GaoDepartment of Medical Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Rudong LiDepartment of Medical Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Farzaneh BehzadniaDepartment of Medical Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Sarah C NabingerDepartment of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
David A SchmitzDepartment of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Hongxia ChenDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Wenjie CaiDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Shiyu XiaoDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Ruyue LuoDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Mohammed Abdullahel AminDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Maegan L CapitanoDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
James P RopaDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Aidan FaheyDepartment of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Shuyi ZhouPrecision Research Center for Refractory Diseases, Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Tiffany M MaysDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Magdalena SoteloDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Hao PanDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Sophie K HuDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Sophia VerangaDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Moiez AliDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Maria ShumilinaDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Reuben KapurDepartment of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Kehan RenDepartment of Pathology and.
Yuzhi JiaDepartment of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Huiping LiuDepartment of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Irum KhanDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Yasmin AbazaDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Jessica K AltmanDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Elizabeth A EklundDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Lucy A GodleyDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Christine R ZhangDepartment of Pathology and.
Peng JiDepartment of Pathology and.
Seth L MastersThe Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Ben A CrokerDepartment of Pediatrics, University of California San Diego, La Jolla, California, USA.
H Scott BoswellDepartment of Medicine and.
George E SanduskyDepartment of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Zhonghua GaoDepartment of Biochemistry and Molecular Biology, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania, USA.
Lindsey D MayoDepartment of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Sharon A SavageClinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
Stephanie HaleneDepartment of Internal Medicine and Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut, USA.
Yali DouDepartment of Medicine, University of Southern California, Los Angeles, California, USA.
Leonidas C PlataniasDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Madina SukhanovaDepartment of Pathology and.
Yunlong LiuDepartment of Medical Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Omar Abdel-WahabMolecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Yan LiuDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4MProject-005U54DK106846 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI Reuben Kapur, Karen Elizabeth Pollok · 2015 to 2026
$9.7MMolecular mechanism underlying clonal expansion of hematopoietic stem cellsR01HL150624 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Yan Liu · 2019 to 2026
$3.8MDysregulated epigenetic control in leukemogenesisR01CA298152 · NCI · NORTHWESTERN UNIVERSITY · PI Yan Liu, MADINA SUKHANOVA · 2025 to 2026
$1.3MNU-TRIHO (Northwestern University Translational Research in Hematology-Oncology) Training ProgramT32CA268935 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI MAHA H HUSSAIN, Hidayatullah G. Munshi · 2023 to 2026
$985kMutant p53 rejuvenates aged stem cells through modulating epigenetic regulatorsR56AG052501 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI LIU, YAN · 2017 to 2017
$255kMolecular mechanisms underlying clonal expansion of hematopoietic stem cellsR56DK119524 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI LIU, YAN · 2018 to 2018
$150kNCI NIH HHS P30 CA008748NCI NIH HHS R01 CA298152NCI NIH HHS T32 CA268935NHLBI NIH HHS R01 HL150624NIA NIH HHS R56 AG052501NIDDK NIH HHS R56 DK119524NIDDK NIH HHS U54 DK106846
Abstract
Older individuals with somatic TP53 mutations manifest clonal hematopoiesis (CH) and are at high risk of developing myeloid neoplasms. However, the underlying mechanisms are not fully understood. Here, we show that inflammatory stress confers a competitive advantage to p53 mutant hematopoietic stem and progenitor cells (HSPCs) by activating the NLRP1 inflammasome and increasing the secretion of pro-inflammatory cytokines such as IL-1β, inhibiting WT HSPC fitness in a paracrine fashion. During aging, mutant p53 dysregulates pre-mRNA splicing in HSPCs, leading to enhanced NF-κB activation and increased secretion of IL-1β and IL-6, thereby generating a chronic inflammatory bone marrow microenvironment. Furthermore, blocking IL-1β with IL-1β neutralizing antibody or inhibiting IL-1β secretion using gasdermin D inhibitor decreases the fitness of p53 mutant HSPCs. Thus, our findings uncover an important role for mutant p53 in regulating inflammatory signaling in CH and suggest that curbing inflammation may prevent the progression of TP53-mutant CH to myeloid neoplasms.
Indexed as
Clonal HematopoiesisHematopoietic Stem CellsInflammationMutationTumor Suppressor Protein p53AnimalsChronic DiseaseHumansInflammasomesInterleukin-1betaInterleukin-6MiceNF-kappa BIL1B protein, humanInflammasomesInterleukin-1betaInterleukin-6NF-kappa BTP53 protein, humanTrp53 protein, mouseTumor Suppressor Protein p53CytokinesHematologyHematopoietic stem cellsInflammationNF-kappaB
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