Clonal hematopoiesis:a shared risk factor for cardiovascular diseases and tumors

Ling-Feng Zha ,Xiang Cheng,＊

Abstract Clonal hematopoiesis (CH) is a clonally expanded population of hematopoietic stem cells carrying somatic mutations that differentiate through multilineage hematopoiesis to form terminally differentiated mature hematopoietic cells carrying markers of the clonal mutation.Genes integral to critical cellular processes such as epigenetic regulation,DNA damage response,and inflammation frequently carry these mutations.Clonal hematopoiesis becomes increasingly prevalent with age and is associated with an increased risk of hematological tumors and some nonhematological conditions.Recent insights have revealed that the mutations driving CH are not only implicated in hematologic neoplasms but also possess the potential to influence cardiovascular pathogenesis.Here,we reviewed up-to-date findings about the roles of CH in cardiovascular diseases and tumors and explored the clinical significance of CH,as well as look forward to future related studies,so as to provide valuable references for future research and clinical practice.

Keywords: Cardiovascular diseases;Clonal hematopoiesis;Tumors

1.Introduction

Clonal hematopoiesis (CH) stands as a captivating and intricate phenomenon within the realm of hematological research,offering a unique perspective into the dynamics of blood cell development and its implications for health and disease.This fascinating process centers around a distinct population of blood cells,all stemming from a single ancestral cell,housing genetic mutations that bestow a selective advantage upon these cells,thereby initiating their unbridled clonal expansion.[1]These mutations,predominantly acquired by hematopoietic stem or progenitor cells,orchestrate a remarkable growth or survival advantage,propelling the affected cells to outcompete their normal counterparts within the complex microenvironment of the bone marrow and peripheral blood.[2]Interestingly,this initial clonal expansion often occurs in an asymptomatic manner,evading clinical detection and emerging unexpectedly during genetic assessments.[3]However,this concealed proliferation has been unequivocally linked to an increased predisposition to a spectrum of hematologic malignancies,including myelodysplastic syndromes,acute myeloid leukemia,and a variety of other perplexing blood disorders.[4,5]Clonal hematopoiesis increases the relative risk of hematological malignancy(hazard ratio[HR],13),[1,6]and is associated with a 0.5% to 1.0%risk per year of leukemia.[5]A comprehensive exploration of the mutations implicated in CH reveals a recurring association with genes pivotal to epigenetic regulation,DNA damage response,and an array of other intricate cellular processes.

Clonal hematopoiesis itself is only considered a precancerous condition,yet evidence suggests that it may have a variety of adverse effects on human health.[7]Early epidemiologic studies noted that CH increased the risk of death by 40%,a magnitude far greater than could be explained by the risk of hematologic malignancy alone.Cohort analyses show that CH increased risk of coronary artery disease (HR,1.8–2.0),ischemic stroke (HR,2.6),diabetes mellitus(HR,3.0),and premature myocardial infarction(HR,4.0)independent of the traditional risk factors for cardiovascular disease(CVD).[6,8]However,it needs to be stressed that the conversion from CH to hematological malignancy is a much more likely event than the development of CVD in the presence of CH.The aim of this review is to explore the association between CH and CVDs and tumors,to summarize the current research progress in this field,to explore the clinical significance of CH,and to look forward to future related studies,so as to provide valuable references for future research and clinical practice.

2.CH definitions

The classification and diagnosis of CH encompass a complex landscape,characterized by diverse definitions and criteria that underscore the intricate nature of this phenomenon.[9]These diagnostic parameters inherently involve a spectrum of considerations,spanning from the specific type and abundance of mutations to the allelic frequency of the mutated cells,culminating in an evaluation of the latent potential for malignant progression.[10]Clearly,the field of CH is in a state of constant evolution,as researchers continuously refine these diagnostic frameworks in response to the expanding understanding of this intricate process.Although the link between CH and an increased susceptibility to hematologic malignancies is well-established,it is crucial to acknowledge that not all cases of CH follow the perilous trajectory toward malignancy.[11]Vigilant monitoring and prudent clinical oversight emerge as indispensable pillars in the management of individuals with CH,offering a powerful toolkit to detect any incipient signs of malignant transformation and promptly initiate therapeutic interventions to avert adverse outcomes.

The molecular mechanisms underpinning CH's initiation and progression are an area of intense investigation.[12]Genetic mutations occurring within hematopoietic stem or progenitor cells can lead to dysregulation in various signaling pathways,including those involved in cell growth,differentiation,and survival.[13]Mutations in genes related to epigenetic regulation,such as DNMT3A and TET2,contribute to abnormal DNA methylation patterns,impacting gene expression and cellular function.[14,15]Other mutations,such as those affecting genes in the DNA damage response pathway(eg,TP53),can lead to genomic instability and increased susceptibility to further mutations.Moreover,the inflammatory microenvironment within the bone marrow and peripheral blood plays a crucial role in CH.Inflammation-driven signaling pathways,such as nuclear factor κB and JAK/STAT,are implicated in the expansion of mutant clones.[16]Inflammatory cytokines and growth factors create a niche that promotes the survival and proliferation of mutant hematopoietic cells,driving clonal expansion.[17–19]

In conclusion,CH continues to unravel its complex secrets,shedding light on the intricate interplay between genetic mutations,cellular dynamics,and disease predisposition.The evolving understanding of its molecular mechanisms and signaling pathways not only enhances our knowledge of hematopoiesis but also holds promise for innovative therapeutic interventions.Targeted interventions aimed at modulating specific signaling pathways,such as inhibitors of inflammatory cytokines or epigenetic modifiers,could be explored to mitigate the expansion of mutant clones and reduce the risk of malignant transformation.

3.CH as a risk factor for tumors

Although CH might initially manifest as an inconspicuous discovery,the genetic alterations it harbors could serve as precursors to oncogenic transformation,thereby contributing to the initiation and progression of tumors.[20]Clonal hematopoiesis has transcended its initial association with hematologic malignancies to emerge as a compelling risk factor for a diverse array of tumors.[20]Compelling epidemiological evidence has firmly linked CH to an escalated tumor risk.Specific mutations frequently associated with CH have been recognized as risk factors for the development of myeloid malignancies.[21]Approximately 80%of patients with CH have mutations in epigenetic regulators DNMT3A,TET2,ASXL1;DNA damage repair genes PPM1D and TP53;the regulatory tyrosine kinase JAK2;or mRNA spliceosome components SF3B1 and SRSF2.[22]Intriguingly,the scope of tumor risk extends beyond hematologic neoplasms,[3]encompassing a spectrum of solid tumors,including lung,colorectal,and bladder cancers.[23]It was shown that 25% of patients with solid cancer harbor 1 or more somatic mutations consistent with CH.[24]

The intricate interplay between CH and tumors entails multifaceted molecular mechanisms.Chronic inflammation incited by mutations linked to CH is believed to foster a microenvironment conducive to tumor growth.[25]Moreover,certain CH-associated mutations might act as the initiating events in a 2-hit model of carcinogenesis,propelling the transformation of precursor cells into malignantly altered counterparts.

The implications of CH as a tumor risk factor are profound,spanning diagnostics and therapeutics.The presence of CH-associated mutations could potentially serve as a valuable biomarker for identifying individuals with an elevated risk of tumors.Routine genetic assessments may incorporate CH screening,facilitating the identification of those who could benefit from heightened surveillance or early intervention strategies.Furthermore,deciphering the role of CH in tumors'development could pave the way for targeted therapies aimed at intercepting the progression from CH to overt malignancy.

Although the link between CH and tumors gains clarity,numerous enigmas remain.Factors influencing the transition from CH to malignancy,the impact of CH on tumors' evolution,and its intricate interactions with genetic and environmental determinants are active focal points of investigation.As the landscape unfolds,an enhanced understanding of the intricate molecular mechanisms entwining CH and tumor promises novel insights into oncogenic processes and potentially redefines tumor risk assessment and management strategies.

In conclusion,the exploration of CH has transcended its initial characterization,positioning it as a significant risk factor for cancer across diverse organ systems.The genetic mutations shaping CH's landscape seem to exert a pivotal influence on oncogenesis,spanning hematologic and solid tumors.As research in this realm burgeons,unraveling the intricate relationship between CH and tumors holds the promise of illuminating innovative avenues for early detection,risk stratification,and personalized therapeutic interventions.

4.CH as a risk factor for CVDs

Clonal hematopoiesis,a phenomenon historically linked to hematologic malignancies,has emerged as a subject of intense investigation for its potential role as a risk factor for CVD.[26]Although the understanding of CH's involvement in malignancies has deepened,its newfound association with cardiovascular health has sparked a captivating avenue of research,shedding light on the complex interplay between hematopoiesis and cardiovascular pathophysiology.[27]Recent insights have revealed that the mutations driving CH are not only implicated in hematologic neoplasms but also possess the potential to influence cardiovascular pathogenesis.[28]Epidemiological studies have consistently indicated an elevated risk of adverse cardiovascular events in individuals with CH.[29]However,unraveling the mechanistic underpinnings of this association remains a dynamic area of investigation.Researchers are delving into intricate molecular pathways that bridge CH-associated mutations and the initiation and progression of CVD.Understanding how these mutations modulate cellular functions,inflammation,and vascular integrity will provide insights into the mechanistic crosstalk between CH and CVD.

The intricate connection of CH with conventional CVD risk factors,such as hypertension,dyslipidemia,and diabetes,adds complexity to its role in cardiovascular health.[30]Comprehensive exploration of how these factors synergize with CH is essential for a holistic understanding of the interplay.Elucidating how CH-associated mutations interact with established cardiovascular risk factors will contribute to a nuanced comprehension of disease pathogenesis and the identification of potential therapeutic targets.

Mounting evidence suggests a bidirectional relationship between CH and CVD,[31,32]with chronic inflammation acting as a key mediator.[33]The inflammatory microenvironment triggered by CH could serve as a bridge that connects these seemingly disparate entities.[34]This chronic inflammation not only contributes to the progression of atherosclerosis,a hallmark of CVD,but it may also exert a reciprocal influence on hematopoietic cell expansion,potentially perpetuating a self-amplifying loop.The intricate interplay between inflammation,CH,and CVD underscores the need for a comprehensive exploration of this multifaceted interaction.[22,35]As research into CH's role in cardiovascular health progresses,it is becoming evident that the molecular mechanisms underpinning this association offer potential targets for therapeutic intervention.Precision medicine approaches that leverage our understanding of CH-associated mutations could pave the way for novel treatment strategies.Modulating the inflammation triggered by CH and targeting key signaling pathways implicated in both CH and CVD might offer avenues for mitigating cardiovascular risk.

The emerging link between CH and CVD unveils a new dimension in the realm of cardiovascular health.As we delve deeper into the molecular mechanisms and signaling pathways connecting CH and CVD,opportunities for innovative preventive and therapeutic strategies come to light.The bidirectional interplay,inflammatory microenvironment,and synergy with conventional risk factors underscore the complexity of this relationship.Although many questions remain unanswered,the ongoing research holds promise for unraveling the intricate connections between hematopoiesis and cardiovascular health,potentially leading to novel interventions that mitigate cardiovascular risk in individuals with CH.

5.CH and CVD in tumor survivors

Cardiovascular diseases and tumors are among the top 3 chronic noncommunicable diseases,and with the development of oncology diagnostic and treatment technologies,the survival period of patients has been significantly prolonged,and the proportion of combined CVDs has been significantly increased.[36]In addition,the cardiovascular damage brought about by antitumor therapy has contributed to a significant increase in the incidence of cardiovascular events,triggering controversy and reflection on the evaluation of the cardiovascular safety of antitumor therapy.[37]

The emergence of CH as a significant player in CVDs has rippled beyond hematologic malignancies,particularly in the realm of cancer survivors.[38]This intersection among CH,cancer,and cardiovascular health elucidates the intricate web of these interconnected conditions,demanding tailored management strategies and holistic care for those who have triumphed over cancer.[39]

Cancer survivors,an increasingly heterogeneous group marked by diverse treatment trajectories,genetic variations,and potential long-term health repercussions,require nuanced health management.As their numbers burgeon owing to advances in cancer therapies,an in-depth comprehension of the latent risks associated with CH becomes imperative.Recent investigations suggest a plausible link between CH and elevated CVD risk,thereby adding a new dimension to the postcancer health narrative.[36]

Cancer treatments,encompassing chemotherapy and radiation,can exert profound influences on the bone marrow and hematopoietic system.[24]The genetic mutations steering CH could be exacerbated by these therapies,potentially fostering the amplification of mutated clones carrying cardiovascular implications.[40]Notably,research highlights that CH-associated mutations are not confined to blood cells alone;they can extend their reach to endothelial cells,precipitating endothelial dysfunction and instigating a proinflammatory and prothrombotic microenvironment.Moreover,cancer survivors often grapple with an amalgamation of CVD risk factors,including shifts in lifestyle,metabolic perturbations,and heightened inflammation.The synergy between CH-related genetic mutations and these external determinants could synergistically propel CVD development in this cohort.Consequently,cancer survivors harboring CH might necessitate vigilant cardiovascular monitoring and targeted interventions to ameliorate the likelihood of cardiovascular events.

The implications of CH in cancer survivors extend beyond risk assessment.Unraveling the intricate interplay between CH,cancer,and CVD could have pronounced implications for treatment choices and survivorship care strategies.[41]Genetic testing aimed at detecting CH mutations might aid in stratifying risk,thereby guiding personalized interventions aimed at mitigating the burden of cardiovascular complications in cancer survivors.[42]However,several queries and challenges persist.The precise molecular mechanisms underscoring the link between CH and CVD in cancer survivors demand further exploration.In addition,formulating optimal strategies for surveillance,prevention,and management of cardiovascular complications in this group presents a multifaceted clinical conundrum.Rigorous research is pivotal in assessing the clinical utility of CH screening and forging evidence-based guidelines for fortifying cardiovascular health in cancer survivors.

In conclusion,the convergence of CH,cancer,and CVD within the context of cancer survivors unveils a multifarious and evolving landscape.The latent capacity of CH to contribute to CVD risk in individuals who have conquered cancer underscores the significance of comprehensive survivorship care,encompassing not only oncologic history but also broader health implications.By unraveling the intricate threads that connect CH,cancer,and CVD,health care practitioners can pave the way for enhanced long-term outcomes and quality of life for cancer survivors.

6.Clinical implications of CH

The clinical implications of CH are multifaceted and continue to evolve as our understanding of this phenomenon deepens.[14]Clonal hematopoiesis,characterized by the presence of genetically mutated blood cells derived from a single ancestral cell,has significant implications across various medical disciplines,from oncology to cardiology.Its recognition and management hold the potential to impact disease diagnosis,treatment decisions,and patient outcomes.[43]

6.1.Oncology and hematology

Clonal hematopoiesis has emerged as a significant area of interest within oncology and hematology.It has been associated with an increased risk of hematologic malignancies,particularly myelodysplastic syndrome and acute myeloid leukemia.The presence of CH mutations can serve as a predictive marker for these diseases,aiding in early detection and intervention.[44]Furthermore,the identification of specific mutations in CH can influence treatment decisions and prognosis,potentially leading to tailored therapeutic approaches.[45]Research is ongoing to explore the intricate relationship between CH and the development of hematologic malignancies,with the goal of improving patient outcomes.

6.2.Cardiovascular health

Recent studies have illuminated a novel link between CH and CVD.Certain CH-associated mutations have been associated with an increased risk of atherosclerotic events,coronary artery disease,and stroke.The underlying mechanisms connecting CH to CVD are being investigated,including the potential impact of mutated blood cells on inflammation and vascular function.This newfound association highlights the importance of a multidisciplinary approach in patient care,where cardiologists and hematologists collaborate to manage both CVD risk and hematologic health.Although the clinical practice of CH in the cardiovascular field is still in its infancy,with the attention of more and more clinicians,a series of clinical studies have been carried out by researchers,and some preliminary research results have been achieved.These results will provide a theoretical basis for the clinical application of CH in the future.In fact,early data from the CANTOS trial revealed that patients with a TET2 mutation had an improved response to canakinumab as evidenced by the decrease in major adverse cardiovascular events,[46]raising the hypothesis that specific mutations may dictate specific treatments in patients.Additional supporting evidence comes from the UK Biobank,where a genetic proxy of interleukin 6 receptor inhibition(presence of the IL6R D358A variant)reduced the risk of cardiovascular events in individuals with DNMT3A or TET2 CH with a large clone size(defined as ＞10%variant allele frequency)back to the baseline of non-CH carriers.[47]These studies may provide valuable knowledge to help direct future treatments for patients with CH.

6.3.Cancer survivorship

For cancer survivors,the implications of CH extend beyond initial treatment.The exposure to chemotherapy and radiation therapy can contribute to the development or expansion of CH clones,potentially increasing the risk of secondary hematologic malignancies.[48]Long-term monitoring of survivors for the presence of CH mutations is crucial,as it may influence the choice of follow-up care and surveillance strategies.[49]Oncologists and hematologists must navigate the delicate balance between addressing the survivor's primary cancer and mitigating the risk of subsequent malignancies arising from CH.

6.4.Genetic counseling and testing

The integration of CH assessment into routine clinical practice raises important ethical and counseling considerations.[42]Patients with CH mutations may benefit from genetic counseling to comprehend the implications for their health and familial inheritance.[50]Genetic testing for CH could potentially become a standard component of health assessments,particularly for individuals with a family history of hematologic malignancies.This approach aligns with the principles of precision medicine,where genetic information guides personalized medical decisions.Specialized CH clinics using multidisciplinary teams(oncologists,hematologists,cardiologists,medical geneticists)are now seeing patients with CH and advising them on the cardiovascular and hematologic risks associated with CH.[51,52]

6.5.Therapeutic opportunities

Although CH is associated with an increased risk of disease,it also presents therapeutic possibilities.Targeted therapies designed to specifically address CH-related mutations are being explored.By developing interventions that selectively target and eliminate mutated cells,researchers aim to reduce the risk of malignancies and associated health complications.These emerging treatment strategies hold promise for improving the long-term health outcomes of individuals with CH.

6.6.Precision medicine and personalized care

The concept of precision medicine revolves around tailoring medical decisions and treatments to each patient's unique genetic profile.Clonal hematopoiesis fits seamlessly into this framework by providing valuable genetic insights that inform clinical management.From predicting disease progression to guiding treatment selection,CH status contributes to personalized care plans that optimize patient outcomes.

In conclusion,the clinical implications of CH span multiple domains of medicine,influencing disease diagnosis,treatment decisions,and survivorship care.[53]From oncology to cardiology,CH underscores the interconnectedness of various medical disciplines.The field of CH is dynamic and rapidly evolving.Ongoing research is crucial to fully understand the clinical implications of CH and to establish evidence-based guidelines for its management.The integration of CH assessment into clinical practice reflects a pivotal step toward precision medicine,where genetic insights empower physicians to deliver personalized and optimized patient care.Collaborative efforts across medical specialties will be pivotal in harnessing the potential of CH information to enhance patient care and shape the future of medical practice.

7.Prevention and therapy of CH

As the understanding of CH continues to evolve,exploring avenues for prevention and therapeutic intervention,especially in the context of CVD,has gained significance.Although the clinical implications of CH have become increasingly evident,strategies to mitigate its impact on cardiovascular health are still in their infancy.Here,we outline potential future directions for CH prevention and therapy with a specific focus on reducing cardiovascular risk.

7.1 Early detection and risk stratification

Developing robust and clinically applicable methods for early detection and risk stratification of CH-associated CVD is essential.Future research could focus on identifying specific CH mutations that confer a higher risk of cardiovascular events.This could enable targeted monitoring and intervention for individuals at greater risk,optimizing preventive strategies.

7.2.Personalized treatment approaches

Precision medicine has the potential to revolutionize CH therapy in the context of CVD.Future studies may investigate individualized treatment plans based on the mutational profile of CH,aiming to counteract the cardiovascular effects of clonally expanded cells.Tailored therapies could range from pharmacological interventions to gene editing techniques.[54]

7.3.Targeting inflammation and immune responses

Given the emerging role of inflammation in both CH and CVD,therapeutic strategies could focus on modulating the immune response.[55]Future research might explore novel immunomodulatory agents that specifically target CH-associated clones and dampen inflammation-driven cardiovascular complications.[56]

7.4.Repurposing cardiovascular medications

Investigating the potential of existing cardiovascular medications for CH management is an intriguing avenue.Certain drugs that have shown efficacy in cardiovascular risk reduction may also impact CH.[46]Repurposing such medications could offer a dual benefit of managing CH and mitigating cardiovascular risk.

7.5.Lifestyle interventions

Lifestyle modifications have a significant impact on cardiovascular health.Future studies could explore whether specific lifestyle interventions,such as diet,exercise,and stress reduction,influence the clonal expansion of hematopoietic cells and subsequently reduce cardiovascular risk in individuals with CH.

7.6.Clinical trials and therapeutic innovation

Conducting clinical trials specifically designed to evaluate CH-targeted therapies for reducing cardiovascular risk is paramount.[56]These trials could explore novel therapeutic agents,dosing regimens,and treatment combinations,aiming to establish evidence-based interventions.

7.7.Patient education and empowerment

Empowering patients with knowledge about their CH status and its potential cardiovascular implications is essential.Future directions could involve developing educational materials and tools that inform patients about the link between CH and CVD,enabling them to actively participate in their preventive and therapeutic strategies.

In conclusion,the evolving landscape of CH prevention and therapy in the context of CVD holds promise for improving patient outcomes.Future directions should prioritize early detection,personalized treatment approaches,innovative therapeutic strategies,and multidisciplinary collaboration.By addressing these avenues,researchers and clinicians can work toward reducing the burden of CVD in individuals with CH.

8.Knowledge gaps and future directions

Although significant progress has been made in understanding CH and its clinical implications,several knowledge gaps remain that warrant further investigation.These gaps present exciting opportunities for future research that could lead to improved patient care and outcomes.[57]Here,we outline some of these knowledge gaps and propose potential future directions for advancing our understanding of CH.

8.1.Mechanistic insights

Although we have identified associations between CH and various diseases,the underlying molecular mechanisms linking CH to these conditions are not fully elucidated.Future research should focus on unraveling the intricate pathways and processes through which clonally expanded cells contribute to disease development.This may involve exploring the role of CH-associated mutations in modulating cellular functions,such as inflammation,immune response,and tissue remodeling.The emerging connection between CH and CVD demands further investigation.Future studies should delve into the mechanisms by which CH mutations contribute to atherosclerosis,thrombosis,and other cardiovascular events.[58]This knowledge could lead to the development of targeted interventions to mitigate CVD risk in individuals with CH.

8.2.Predictive biomarkers

Clonal hematopoiesis mutations have shown promise as predictive biomarkers for hematologic malignancies.However,more research is needed to refine the predictive value of specific mutations and their combinations.[59]Prospective studies could assess the long-term risk associated with different CH mutations and develop risk stratification models that guide clinical decision-making.

8.3.Therapeutic strategies

The potential therapeutic implications of CH mutations extend beyond risk assessment.[60]Investigating targeted therapies that specifically target and eliminate clonally expanded cells holds promise for preventing hematologic malignancies and associated complications.Developing precision medicine approaches that leverage CH mutational profiles could revolutionize treatment strategies.

8.4.Survivorship care

As the population of cancer survivors grows,understanding the impact of CH on survivorship becomes paramount.Longitudinal studies are needed to assess how CH mutations evolve over time in cancer survivors and whether they influence the risk of treatment-related secondary malignancies.Implementing tailored surveillance strategies based on CH status could optimize survivorship care.

8.5.Multidisciplinary collaboration

The complex interplay of CH with various diseases necessitates collaboration across medical disciplines.Integrating expertise from oncology,hematology,cardiology,genetics,and other fields can provide a holistic understanding of CH-related pathophysiology.Collaborative efforts could lead to innovative diagnostic and therapeutic approaches.

8.6.Ethical considerations

The integration of CH assessment into routine clinical practice raises ethical questions related to genetic testing,counseling,and patient autonomy.As interventions for CH prevention and therapy advance,addressing ethical considerations becomes imperative.Future efforts should ensure that potential risks,benefits,and uncertainties associated with CH-targeted interventions are communicated transparently to patients,enabling informed decision-making.

8.7.Long-term outcomes

While CH's association with disease risk is well-established,the long-term outcomes of individuals with CH who do not progress to malignancy require investigation.Understanding the health trajectories of these individuals can provide insights into the broader clinical significance of CH and guide appropriate follow-up strategies.[61]Longitudinal studies are crucial to understanding the natural progression of CH-associated CVD and the impact of interventions over time.Establishing cohorts of individuals with CH and cardiovascular comorbidities could provide insights into the long-term effects of various therapeutic approaches.

In conclusion,CH is a rapidly evolving field with far-reaching clinical implications.As we strive to bridge existing knowledge gaps,researchers have the opportunity to advance our understanding of CH's molecular underpinnings,refine predictive biomarkers,explore therapeutic strategies,and optimize survivorship care.By fostering multidisciplinary collaboration and addressing ethical considerations,the medical community can harness the potential of CH information to improve patient outcomes and transform the landscape of personalized medicine.

9.Conclusions

Clonal hematopoiesis is an intricate and dynamic phenomenon that has transcended its origins as a precursor to hematologic malignancies.Its far-reaching implications span across oncology,cardiology,survivorship care,and the realm of precision medicine.The recognition of CH mutations as potential predictive markers has transformed the landscape of disease diagnosis and risk stratification,guided therapeutic decisions,and influenced prognosis.As our understanding deepens,CH mutations hold the potential to become integral components of precision medicine,enabling tailored interventions that optimize patient outcomes.

Moreover,the newfound link between CH and CVD introduces a paradigm shift in our approach to cardiovascular health.The intersections between CH-associated mutations and mechanisms implicated in CVD pathogenesis underscore the intricate interplay between hematologic and cardiovascular systems.By harnessing this knowledge,health care providers can proactively identify individuals at elevated risk for cardiovascular events and implement targeted strategies to mitigate these risks.The integration of CH assessment into clinical practice is a testament to the transformative potential of precision medicine in optimizing cardiovascular care.

In the realm of survivorship,CH takes on a novel role as a potential determinant of long-term health outcomes for cancer survivors.The delicate balance between addressing the aftermath of cancer treatment and managing the risk of subsequent hematologic neoplasms adds a layer of complexity to survivorship care.Future research in this area will undoubtedly refine our understanding of CH's role in survivorship and inform tailored surveillance strategies that prioritize both oncologic and cardiovascular health.

Looking ahead,the landscape of CH research is rich with untapped potential.The identification of specific CH mutations as therapeutic targets opens the door to innovative treatment strategies that disrupt the progression of hematologic malignancies and associated complications.Collaborative efforts across diverse medical disciplines will be instrumental in realizing the full therapeutic potential of CH-associated mutations.As we navigate this evolving landscape,ethical considerations and patient education remain paramount.Transparent communication of the implications,benefits,and potential risks of CH assessment and interventions will empower patients to make informed decisions about their health.

In conclusion,the exploration of CH has illuminated its multifaceted impact on disease pathogenesis,risk stratification,and therapeutic approaches.From predictive biomarkers to personalized treatment strategies,the integration of CH information into clinical practice represents a pivotal advancement in the pursuit of precision medicine.By addressing the knowledge gaps,embracing multidisciplinary collaboration,and prioritizing patient-centered care,the medical community is poised to harness the potential of CH for the betterment of patient outcomes and the advancement of medical science.

Acknowledgments

The authors are very grateful and thank all participations and support in this study.

Financial support and sponsorship

Supported by a grant from the National Natural Science Foundation of China(no.82200319).

Conflicts of interest statement

X.Cheng is an editorial board member of Oncology and Translational Medicine.This article is subject to the journal's standard procedures,with peer review handled independently of the relevant editorial board member and his/her research groups.

Author contributions

L.-F.Zha and X.Cheng provided ideas;L.-F.Zha wrote the manuscript;L.-F.Zha and X.Cheng revised the manuscript.Both authors reviewed the manuscript and agreed to publish.

Data availability statement

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Ethical approval

Not applicable.