Connections Between Clonal Hematopoiesis, Cardiovascular Disease, and Cancer

Calvillo‐Argüelles, Oscar; Jaiswal, Siddhartha; Shlush, Liran I.; Moslehi, Javid; Schimmer, Aaron D.; Barac, Ana; Thavendiranathan, Paaladinesh

doi:10.1001/jamacardio.2019.0302

Cited by 45 publications

(33 citation statements)

References 67 publications

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“…Most of these mutations have little or no effect on normal cell physiology, but eventually, some of them could provide a selective advantage to the hematopoietic cell in which they occur. The result is a clonal expansion in the peripheral blood since the mutated stem cells maintain the ability to differentiate into granulocytes, monocytes, and lymphocytes [11][12][13][14][15][16][17].…”

Section: Passenger Mutationmentioning

confidence: 99%

“…Other main features of CHIP include the absence of morphological variation in the blood cells as well as diagnostic criteria for symptoms currently associated with hematological cancer (for example, gammopathy) [ 13 , 14 ]. The prevalence of CHIP varies with age, ranging from less than 1% in those younger than 40 years, to more than 15% in those 90 years and older [ 12 , 18 , 19 ]. Generally, the clonal mosaicism for a large chromosomal abnormality, reflecting the expansion of a specific cell clone, appears to arise in approximately 2% of the elderly population [ 20 ].…”

Section: Age-related Clonal Hematopoiesis and Cancermentioning

confidence: 99%

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Translating Evidence from Clonal Hematopoiesis to Cardiovascular Disease: A Systematic Review

Papa

Marracino

Fortini

et al. 2020

JCM

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Some random mutations can confer a selective advantage to a hematopoietic stem cell. As a result, mutated hematopoietic stem cells can give rise to a significant proportion of mutated clones of blood cells. This event is known as “clonal hematopoiesis.” Clonal hematopoiesis is closely associated with age, and carriers show an increased risk of developing blood cancers. Clonal hematopoiesis of indeterminate potential is defined by the presence of clones carrying a mutation associated with a blood neoplasm without obvious hematological malignancies. Unexpectedly, in recent years, it has emerged that clonal hematopoiesis of indeterminate potential carriers also have an increased risk of developing cardiovascular disease. Mechanisms linking clonal hematopoiesis of indeterminate potential to cardiovascular disease are only partially known. Findings in animal models indicate that clonal hematopoiesis of indeterminate potential-related mutations amplify inflammatory responses. Consistently, clinical studies have revealed that clonal hematopoiesis of indeterminate potential carriers display increased levels of inflammatory markers. In this review, we describe progress in our understanding of clonal hematopoiesis in the context of cancer, and we discuss the most recent findings linking clonal hematopoiesis of indeterminate potential and cardiovascular diseases.

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Section: Passenger Mutationmentioning

confidence: 99%

Section: Age-related Clonal Hematopoiesis and Cancermentioning

confidence: 99%

Translating Evidence from Clonal Hematopoiesis to Cardiovascular Disease: A Systematic Review

Papa

Marracino

Fortini

et al. 2020

JCM

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“…The prevalence of CH is more common than originally put forward given recent findings from high-depth, high-sensitivity sequencing studies (Young et al 2016;Coombs et al 2017;Abelson et al 2018;Desai et al 2018;Calvillo-Argüelles et al 2019;Young et al 2019). Current evidence suggests mutations of >1% VAF can be of clinical relevance for progression to malignancy (Abelson et al 2018;Desai et al 2018;Young et al 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Understanding CH mutations in the context of these extrinsic influences will enable development of better predictive models to improve decision-making when CH is detected. Although the cardiovascular risks associated with CH are important and considerable and reviewed elsewhere (Sano et al 2018;Calvillo-Argüelles et al 2019), the present review will focus on presenting what is known about the genetics, risks, and possible management strategies for CH in the context of premalignant conditions and hematologic malignancies ( Fig. 1).…”

Section: Mutation Landscape Of Clonal Hematopoiesismentioning

confidence: 99%

Clonal Hematopoiesis and Premalignant Diseases

Kaner

Desai

Mencia-Trinchant

et al. 2019

Cold Spring Harb Perspect Med

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Clonal hematopoiesis (CH) arises when mutations in the hematopoietic system confer a fitness advantage to specific clones, thereby favoring their disproportionate growth. The presence of CH increases with age and environmental exposures such as cytotoxic chemotherapy or radiotherapy. The most frequent mutations occur in epigenetic regulators, such as DNMT3A, TET2, and ASXL1, leading to dysregulation of tumor suppressor function, pathogen response, and inflammation. These dysregulated processes elevate risk of overall mortality, cardiovascular disease, and eventual hematologic malignancy (HM). CH is likely acting as an initiating event leading to HM when followed by cooperating mutations. However, further evidence suggests that CH exerts a bystander influence through its pro-inflammatory properties. Delineating the mechanisms that lead to the onset and expansion of CH as well as its contribution to risk of HM is crucial to defining a management and intervention strategy. In this review, we discuss the potential causes, consequences, technical considerations, and possible management strategies for CH in the context of HMs and pre-HMs.

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“…Of note, administration of the NLRP3 inflammasome inhibitors protected against heart failure and rescued the differences in cardiac performances between wild-type and Tet2-deficient mice (Sano et al 2018). Accordingly, a study conducted on patients affected by acute myeloid leukaemia before chemotherapy treatment demonstrated an association between leukaemia and cardiac alterations (Assuncao et al 2017;Calvillo-Arguelles et al 2019). Whether and how clonal haematopoiesis influences the communication between cancer and cardiac cells is not yet clear, but ongoing studies are expected to soon clarify this unexpected new arm of inflammatory cross-talk.…”

Section: Future Directionsmentioning

confidence: 99%

Mechanisms underlying the cross‐talk between heart and cancer

Brancaccio

Pirozzi

Hirsch

et al. 2019

The Journal of Physiology

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Cardiovascular diseases and cancer remain the leading cause of death worldwide. Despite the fact that these two conditions have long been considered as distinct clinical entities, recent epidemiological and experimental studies suggest that they should be contemplated and treated as co-morbidities. Heart failure represents nowadays a well-established complication of cancer, primarily as a consequence of the aggressive use of cardiotoxic anti-cancer treatments. On the other hand, the provocative idea that heart failure can prime carcinogenesis has started to emerge, though the molecular basis is still to be fully elucidated. This review summarizes the current knowledge on the mechanisms underlying the bidirectional communication between the failing heart and the cancer. We will discuss and/or speculate on the role of molecular mediators released by either the tumour or the heart that can potentially link heart failure and cancer.

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Connections Between Clonal Hematopoiesis, Cardiovascular Disease, and Cancer

Abstract: This narrative review discusses the evidence for clonal hematopoiesis as a physiological factor connecting cancer and cardiovascular disease.

Cited by 45 publications

References 67 publications

Translating Evidence from Clonal Hematopoiesis to Cardiovascular Disease: A Systematic Review

Translating Evidence from Clonal Hematopoiesis to Cardiovascular Disease: A Systematic Review

Clonal Hematopoiesis and Premalignant Diseases

Mechanisms underlying the cross‐talk between heart and cancer

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