Evaluation of clonal hematopoiesis and mosaic loss of Y chromosome in cardiovascular risk: An analysis in prospective studies DOI Creative Commons
Sami Fawaz,

Severine Marti,

Mélody Dufossée

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Dec. 12, 2024

Background: Clonal hematopoiesis of indeterminate potential (CHIP) was initially linked to a twofold increase in atherothrombotic events. However, recent investigations have revealed more nuanced picture, suggesting that CHIP may confer only modest rise myocardial infarction (MI) risk. This observed lower risk might be influenced by yet unidentified factors modulate the pathological effects CHIP. Mosaic loss Y chromosome (mLOY), common marker clonal men, has emerged as candidate for modulating cardiovascular associated with In this study, we aimed ascertain each somatic mutation or mLOY and explore whether could exert an influence on Methods: We conducted examination presence using targeted high-throughput sequencing digital PCR cohort 446 individuals. Among them, 149 patients from CHAth study had experienced first MI at time inclusion (MI(+) subjects), while 297 individuals Three-City no history events (CVE) (MI(-) subjects). All subjects underwent thorough phenotyping, including direct assessment atherosclerotic burden. Our investigation determine inflammation, atherosclerosis burden, Results: were detected substantial prevalence (45.1% 37.7%, respectively), their occurrence similar between MI(+) MI(-) subjects. Notably, nearly 40% CHIP(+) male also exhibited mLOY. Interestingly, neither nor independently resulted significant increases plasma hs-CRP levels, incidence. Moreover, did not amplify diminish atherosclerosis, incidence among Conversely, subjects, heightened over 5 y period, particularly those lacking Conclusions: highlights high elderly Importantly, our results demonstrate isolation substantially contributes Furthermore, find does modulation accelerate MI, especially when unaccompanied These findings underscore complexity interplay CHIP, mLOY, risk, large-scale studies thousands necessary elucidate subtle correlations. Funding: supported Fondation Cœur & Recherche (the Société Française de Cardiologie), Fédération Cardiologie, ERA-CVD (« CHEMICAL » consortium, JTC 2019) Université Bordeaux. The laboratory Hematology University Hospital Bordeaux benefitted convention Nouvelle Aquitaine Region (2018-1R30113-8473520) acquisition Nextseq 550Dx sequencer used study. Clinical trial number: NCT04581057 .

Language: Английский

Clonal Hematopoiesis Associates with Prevalent and Incident Cardiometabolic Disease in High-Risk Individuals DOI Creative Commons
Jessica A. Regan, Lydia Coulter Kwee, Navid A. Nafissi

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Abstract Background Clonal hematopoiesis of indeterminate potential (CHIP) is the age-related presence expanded somatic clones secondary to leukemogenic driver mutations and associated with cardiovascular (CV) disease mortality. We sought evaluate relationships between CHIP cardiometabolic diseases incident outcomes in high-risk individuals. Methods genotyping was performed 8469 individuals referred for cardiac catheterization at Duke University (CATHGEN study) identify variants present a variant allele fraction (VAF) ≥2%. Associations were tested among any variant, large (VAF ≥10%) individual genes prevalent traits. Cox proportional hazard models associations time-to-overall mortality Fine-Gray analyses outcomes. Results identified 463 427 (5.0%) which 268 (3.2%) harbored clones. lower odds obesity (OR 0.79 [95% CI 0.65-0.98], p=0.03; OR 0.76 0.57-0.99], p=0.04, respectively). HF 1.25 1.01 - 1.55], p=0.04; especially non- DNMT3A 1.38 1.04-1.82], p=0.02). also events: Non- increased risk time-to-HF hospitalization (HR 1.29 1.02-1.63], p=0.03). Conclusions In catheterization, DNTM3A obesity, HF, CV events. These findings strengthen importance as biomarker highlight contributing variants. Condensed CHIP, myeloid hematopoietic cells, an emerging CVD biomarker. Using whole exome sequencing peripheral blood derived DNA from participants CATHGEN cohort, we significant mortality, AF after adjusting established clinical factors. add strength growing literature biomarker, emphasizing driving risk. Future studies should aim further elucidate gene-specific inflammatory metabolic mechanisms possibly mediating these relationships. Clinical Perspective What Is New? cohort high prevalence CAD, inversely higher subsequent even adjustment relevant comorbidities. Risk events driven by (VAF≥10%) other than . are Implications? Though more research needed, evidence around specific continues grow, clinicians be prepared provide gene- counseling

Language: Английский

Citations

1
Clonal hematopoiesis, cardiovascular disease and cancer treatment-induced cardiotoxicity DOI

Nan Zhang,

Xu Tian, Dong-Kun Sun

et al.

Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Inflammatory reprogramming of the solid tumor microenvironment by infiltrating clonal hematopoiesis is associated with adverse outcomes DOI Creative Commons
Marco M. Buttigieg, Caitlyn Vlasschaert, Alexander G. Bick

et al.

Cell Reports Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 101989 - 101989

Published: March 1, 2025

Clonal hematopoiesis (CH)-the expansion of somatically mutated hematopoietic cells-is common in solid cancers. CH is associated with systemic inflammation, but its impact on tumor biology underexplored. Here, we report the effects microenvironment (TME) using 1,550 treatment-naive patient samples from Clinical Proteomics Tumor Analysis Consortium (CPTAC) cohort. present 18.3% patients, one-third mutations also detectable tumor-derived DNA same individual (CH-Tum), reflecting CH-mutant leukocyte infiltration. Across cancers, presence CH-Tum worse survival outcomes. Molecular analyses reveal an association between and immune-rich, inflammatory TME that notably distinct age-related gene expression changes. These are most prominent glioblastoma, where correlates pronounced macrophage infiltration, aggressive, mesenchymal phenotype. Our findings demonstrate shapes TME, potential applications as a biomarker precision oncology.

Language: Английский

Citations

0
Clonal haematopoiesis in cardiovascular disease: prognostic role and novel therapeutic target DOI
Art Schuermans, Michael C. Honigberg

Nature Reviews Cardiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Language: Английский

Citations

0
Inflammatory reprogramming of the tumor microenvironment by infiltrating clonal hematopoiesis is associated with adverse outcomes in solid cancer DOI Open Access
Marco M. Buttigieg, Caitlyn Vlasschaert, Alexander G. Bick

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 30, 2024

Abstract Clonal hematopoiesis (CH) – the expansion of somatically-mutated hematopoietic cells in blood is common solid cancers. CH associated with systemic inflammation that may lead to cancer, but its impact on tumor biology underexplored. Here, we report effects microenvironment (TME) using 1,550 treatment-naïve patient samples from CPTAC cohort. was present 18.3% patients, one-third mutations also detectable tumor-derived DNA same individual (CH-Tum), reflecting CH-mutant leukocyte infiltration. The presence CH-Tum worse survival across cancers, particularly for glioblastoma. Transcriptomics and proteomics revealed drives TME a cancer- driver-specific manner, improve immunotherapy responses. In glioblastoma, pronounced macrophage infiltration, inflammation, an aggressive, mesenchymal phenotype. Our findings demonstrate shapes TME, potential applications as biomarker precision oncology.

Language: Английский

Citations

1
Evaluation of Clonal Hematopoiesis and Mosaic Loss of Y Chromosome in Cardiovascular Risk: an analysis in prospective studies DOI Creative Commons
Sami Fawaz, Sara Martí,

Mélody Dufossée

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 17, 2024

Abstract Background Clonal hematopoiesis of indeterminate potential (CHIP) was initially linked to a twofold increase in atherothrombotic events. However, recent investigations have revealed more nuanced picture, suggesting that CHIP may confer only modest rise Myocardial Infarction (MI) risk. This observed lower risk might be influenced by yet unidentified factors modulate the pathological effects CHIP. Mosaic loss Y chromosome (mLOY), common marker clonal men, has emerged as candidate for modulating cardiovascular associated with In this study, we aimed ascertain each somatic mutation or mLOY and explore whether could exert an influence on Methods We conducted examination presence using targeted high-throughput sequencing digital PCR cohort 446 individuals. Among them, 149 patients from CHAth study had experienced first myocardial infarction at time inclusion (MI(+) subjects), while 297 individuals Three-City no history events (CVE) (MI(-) subjects). All subjects underwent thorough phenotyping, including direct assessment atherosclerotic burden. Our investigation determine inflammation, atherosclerosis burden, Results were detected substantial prevalence (45.1% 37.7%, respectively), their occurrence similar between MI(+) MI(-) subjects. Notably, nearly 40% CHIP(+) male also exhibited mLOY. Interestingly, neither nor independently resulted significant increases plasma hsCRP levels, MI incidence. Moreover, did not amplify diminish atherosclerosis, incidence among Conversely, subjects, heightened over five-year period, particularly those lacking Conclusion highlights high elderly Importantly, our results demonstrate isolation substantially contribute Furthermore, find does modulation accelerate MI, especially when unaccompanied These findings underscore complexity interplay CHIP, mLOY, risk, large-scale studies thousands necessary elucidate subtle correlations.

Language: Английский

Citations

0
Evaluation of Clonal Hematopoiesis and Mosaic Loss of Y Chromosome in Cardiovascular Risk: an analysis in prospective studies DOI Creative Commons
Sami Fawaz,

Severine Marti,

Mélody Dufossée

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: May 2, 2024

Background: Clonal hematopoiesis of indeterminate potential (CHIP) was initially linked to a twofold increase in atherothrombotic events. However, recent investigations have revealed more nuanced picture, suggesting that CHIP may confer only modest rise myocardial infarction (MI) risk. This observed lower risk might be influenced by yet unidentified factors modulate the pathological effects CHIP. Mosaic loss Y chromosome (mLOY), common marker clonal men, has emerged as candidate for modulating cardiovascular associated with In this study, we aimed ascertain each somatic mutation or mLOY and explore whether could exert an influence on Methods: We conducted examination presence using targeted high-throughput sequencing digital PCR cohort 446 individuals. Among them, 149 patients from CHAth study had experienced first MI at time inclusion (MI(+) subjects), while 297 individuals Three-City no history events (CVE) (MI(-) subjects). All subjects underwent thorough phenotyping, including direct assessment atherosclerotic burden. Our investigation determine inflammation, atherosclerosis burden, Results: were detected substantial prevalence (45.1% 37.7%, respectively), their occurrence similar between MI(+) MI(-) subjects. Notably, nearly 40% CHIP(+) male also exhibited mLOY. Interestingly, neither nor independently resulted significant increases plasma hs-CRP levels, incidence. Moreover, did not amplify diminish atherosclerosis, incidence among Conversely, subjects, heightened over 5 y period, particularly those lacking Conclusions: highlights high elderly Importantly, our results demonstrate isolation substantially contributes Furthermore, find does modulation accelerate MI, especially when unaccompanied These findings underscore complexity interplay CHIP, mLOY, risk, large-scale studies thousands necessary elucidate subtle correlations. Funding: supported Fondation Cœur & Recherche (the Société Française de Cardiologie), Fédération Cardiologie, ERA-CVD (« CHEMICAL » consortium, JTC 2019) Université Bordeaux. The laboratory Hematology University Hospital Bordeaux benefitted convention Nouvelle Aquitaine Region (2018-1R30113-8473520) acquisition Nextseq 550Dx sequencer used study. Clinical trial number: NCT04581057 .

Language: Английский

Citations

0
Evaluation of Clonal Hematopoiesis and Mosaic Loss of Y Chromosome in Cardiovascular Risk: an analysis in prospective studies DOI Open Access
Sami Fawaz,

Severine Marti,

Mélody Dufossée

et al.

Published: Sept. 27, 2024

Clonal hematopoiesis of indeterminate potential (CHIP) was initially linked to a twofold increase in atherothrombotic events. However, recent investigations have revealed more nuanced picture, suggesting that CHIP may confer only modest rise Myocardial Infarction (MI) risk. This observed lower risk might be influenced by yet unidentified factors modulate the pathological effects CHIP. Mosaic loss Y chromosome (mLOY), common marker clonal men, has emerged as candidate for modulating cardiovascular associated with In this study, we aimed ascertain each somatic mutation or mLOY and explore whether could exert an influence on CHIP.We conducted examination presence using targeted high-throughput sequencing digital PCR cohort 446 individuals. Among them, 149 patients from CHAth study had experienced first myocardial infarction at time inclusion (MI(+) subjects), while 297 individuals Three-City no history events (CVE) (MI(-) subjects). All subjects underwent thorough phenotyping, including direct assessment atherosclerotic burden. Our investigation determine inflammation, atherosclerosis burden, CHIP.CHIP were detected substantial prevalence (45.1% 37.7%, respectively), their occurrence similar between MI(+) MI(-) subjects. Notably, nearly 40% CHIP(+) male also exhibited mLOY. Interestingly, neither nor independently resulted significant increases plasma hsCRP levels, MI incidence. Moreover, did not amplify diminish atherosclerosis, incidence among Conversely, subjects, heightened over five-year period, particularly those lacking mLOY.Our highlights high elderly Importantly, our results demonstrate isolation substantially contribute Furthermore, find does modulation accelerate MI, especially when unaccompanied These findings underscore complexity interplay CHIP, mLOY, risk, large-scale studies thousands necessary elucidate subtle correlations.

Language: Английский

Citations

0
Clonal Hematopoiesis of Indeterminate Potential and Cardiovascular Health DOI
Michael A. Raddatz, Yash Pershad, Alyssa Parker

et al.

Cardiology Clinics, Journal Year: 2024, Volume and Issue: 43(1), P. 13 - 23

Published: Oct. 2, 2024

Language: Английский

Citations

0
Evaluation of clonal hematopoiesis and mosaic loss of Y chromosome in cardiovascular risk: An analysis in prospective studies DOI Creative Commons
Sami Fawaz,

Severine Marti,

Mélody Dufossée

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Dec. 12, 2024

Background: Clonal hematopoiesis of indeterminate potential (CHIP) was initially linked to a twofold increase in atherothrombotic events. However, recent investigations have revealed more nuanced picture, suggesting that CHIP may confer only modest rise myocardial infarction (MI) risk. This observed lower risk might be influenced by yet unidentified factors modulate the pathological effects CHIP. Mosaic loss Y chromosome (mLOY), common marker clonal men, has emerged as candidate for modulating cardiovascular associated with In this study, we aimed ascertain each somatic mutation or mLOY and explore whether could exert an influence on Methods: We conducted examination presence using targeted high-throughput sequencing digital PCR cohort 446 individuals. Among them, 149 patients from CHAth study had experienced first MI at time inclusion (MI(+) subjects), while 297 individuals Three-City no history events (CVE) (MI(-) subjects). All subjects underwent thorough phenotyping, including direct assessment atherosclerotic burden. Our investigation determine inflammation, atherosclerosis burden, Results: were detected substantial prevalence (45.1% 37.7%, respectively), their occurrence similar between MI(+) MI(-) subjects. Notably, nearly 40% CHIP(+) male also exhibited mLOY. Interestingly, neither nor independently resulted significant increases plasma hs-CRP levels, incidence. Moreover, did not amplify diminish atherosclerosis, incidence among Conversely, subjects, heightened over 5 y period, particularly those lacking Conclusions: highlights high elderly Importantly, our results demonstrate isolation substantially contributes Furthermore, find does modulation accelerate MI, especially when unaccompanied These findings underscore complexity interplay CHIP, mLOY, risk, large-scale studies thousands necessary elucidate subtle correlations. Funding: supported Fondation Cœur & Recherche (the Société Française de Cardiologie), Fédération Cardiologie, ERA-CVD (« CHEMICAL » consortium, JTC 2019) Université Bordeaux. The laboratory Hematology University Hospital Bordeaux benefitted convention Nouvelle Aquitaine Region (2018-1R30113-8473520) acquisition Nextseq 550Dx sequencer used study. Clinical trial number: NCT04581057 .

Language: Английский

Citations

0