Clonal hematopoiesis of indeterminate potential: a multisystem hub bridging hematopoietic dysfunction with non-hematopoietic diseases

Jing-Lei Zhang; Shuo-Lan Tong; Qi-Qi Zhuang; Sheng-Jie Jin; Jia-Qiu Li; Jie Sun

doi:10.1186/s40779-025-00654-8

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Clonal hematopoiesis of indeterminate potential: a multisystem hub bridging hematopoietic dysfunction with non-hematopoietic diseases

REVIEW | Updated：2026-05-08

- Clonal hematopoiesis of indeterminate potential: a multisystem hub bridging hematopoietic dysfunction with non-hematopoietic diseases
- Military Medical Research Vol. 13, Issue 3, Pages: 426-446(2026)
- Affiliations：
  
  1.Department of Oncology, Affiliated Hospital of Shandong Second Medical University, Shandong Second Medical University, Weifang 261042, Shandong, China
  2.Zhejiang Key Laboratory for Precision Diagnosis and Treatment of Hematological Malignancies, Hangzhou 310006, China
  3.Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
  4.Department of Biochemistry and Molecular Biology, Monash University, Clayton, Melbourne, VIC 3168, Australia
  5.Clinical Research Center, Affiliated Hospital of Shandong Second Medical University, Shandong Second Medical University, Weifang 261042, Shandong, China
  6.Zhejiang Provincial Clinical Research Center for Hematological Disorders, Hangzhou 310006, China
- Author bio：
  
  * Jia-Qiu Li lijq@sdsmu.edu.cn
  Jie Sun sunjiehm@zju.edu.cn
- Funds：
- DOI：10.1186/s40779-025-00654-8
  CLC：
- Received：04 June 2025，
  
  Accepted：27 September 2025，
  
  Online First：14 October 2025，
  
  Published：2026-03
- Accepted：
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Jing-Lei Zhang, Shuo-Lan Tong, Qi-Qi Zhuang, et al. Clonal hematopoiesis of indeterminate potential: a multisystem hub bridging hematopoietic dysfunction with non-hematopoietic diseases[J]. Military Medical Research, 2026, 13(3): 426-446.
DOI：

Jing-Lei Zhang, Shuo-Lan Tong, Qi-Qi Zhuang, et al. Clonal hematopoiesis of indeterminate potential: a multisystem hub bridging hematopoietic dysfunction with non-hematopoietic diseases[J]. Military Medical Research, 2026, 13(3): 426-446. DOI： 10.1186/s40779-025-00654-8.

摘要

Abstract

Clonal hematopoiesis of indeterminate potential (CHIP)

driven by leukemia-related somatic mutations in hemat-opoietic stem cells

previously recognized as a major risk factor for hematological malignancies

has now emerged as a potent risk factor for chronic inflammation and diverse non-hematologic diseases. CHIP-associated DNA meth-yltransferase 3 alpha (

DNMT3A

)

tet methylcytosine dioxygenase 2 (

TET2

)

and additional sex combs like 1 (

ASXL1

)mutations alter epigenetic programs

skew myelopoiesis

and increase proinflammatory cytokines

resulting in chronic inflammation and immune imbalance. This review integrates mechanistic insights with clinical evidence to deline-ate CHIP’s roles in solid tumors

cardiovascular disorders

and metabolic dysregulation

with an extended discussion of renal dysfunction and neurodegenerative conditions. Furthermore

we also discuss CHIP’s diagnostic and therapeu-tic impacts across multiple disease contexts

advocating for mutation-specific diagnostic paradigms to guide thera-peutic interventions.

关键词

Keywords

references

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