Arteriosclerosis Thrombosis and Vascular Biology, Год журнала: 2024, Номер 44(4), С. 768 - 771
Опубликована: Март 27, 2024
Язык: Английский
Journal of the American College of Cardiology, Год журнала: 2023, Номер 81(20), С. 1996 - 2009
Опубликована: Май 1, 2023
Язык: Английский
Процитировано
64
Immunity, Год журнала: 2024, Номер 57(6), С. 1225 - 1242.e6
Опубликована: Май 14, 2024
Язык: Английский
Процитировано
16
Blood Advances, Год журнала: 2024, Номер 8(14), С. 3771 - 3784
Опубликована: Июнь 5, 2024
With advances in sequencing, individuals with clonal hematopoiesis of indeterminate potential (CHIP) are increasingly being identified, making it essential to understand its prognostic implications. We conducted a systematic review studies comparing the risk clinical outcomes and without CHIP. searched MEDLINE EMBASE included original research reporting an outcome measure CHIP, adjusted for effect age. From 3305 screened, we 88 45 470 960 participants. Most had low-to-moderate bias all domains Quality Prognostic Factor Studies tool. Random-effects meta-analyses were performed reported at least 3 studies. CHIP conferred increased all-cause mortality (hazard ratio [HR], 1.34; 95% confidence interval, 1.19-1.50), cancer (HR, 1.46; 1.13-1.88), composite cardiovascular events 1.40; 1.19-1.65), coronary heart disease 1.76; 1.27-2.44), stroke 1.16; 1.05-1.28), failure 1.27; 1.15-1.41), hematologic malignancy 4.28; 2.29-7.98), lung 1.27-1.54), renal impairment 1.25; 1.18-1.33) severe COVID-19 (odds [OR], 1.18-1.80). was not associated 1.09; 0.97-1.22), except subgroup analysis restricted larger clones 1.31; 1.12-1.54). Isolated DNMT3A mutations did increase myeloid malignancy, mortality, or impairment. The reasons heterogeneity between differences definitions measurements outcomes, populations studied. In summary, is diverse clone size, specific gene, inherent patient characteristics important mediators risk.
Язык: Английский
Процитировано
10
Cardiovascular Diabetology, Год журнала: 2025, Номер 24(1)
Опубликована: Янв. 22, 2025
Both clonal hematopoiesis of indeterminate potential (CHIP) and type 2 diabetes mellitus (T2DM) are conditions closely associated with advancing age. This study delves into the possible implications prognostic significance CHIP T2DM in patients diagnosed ST-segment elevation myocardial infarction (STEMI). Deep-targeted sequencing employing a unique molecular identifier (UMI) for analysis 42 mutations—achieving an impressive mean depth coverage at 1000 × —was conducted on cohort 1430 acute (473 930 non-DM subjects). Variant allele fraction ≥ 2.0% indicated presence mutations. The association between was evaluated by comparison (i) prevalence mutations among individuals versus those without, (ii) clinical characteristics delineated within diabetic (iii) correlation mortality rates subjects. Furthermore, two-sample bidirectional Mendelian randomization performed using genetic instruments from genome-wide TET2 mutation CH UK Biobank (UKB) (2041 cases,173,918 controls) to investigate causal relationship FinnGen consortium (65,085 cases 335,112 controls), vice versa. Most commonly exhibiting variant were identified 50/473 (10.6%) T2DM, demonstrating greater compared subjects [69/930 (7.4%); P < 0.05] across various age groups. After multivariable adjustment, any 2.03-fold higher DM [adjusted hazard ratio (HR) 2.03; 95% confidence interval (CI) 1.07–3.84, 0.05]. In gene-specific analyses, somatic presented highest (adjusted HR 5.24; CI 2.02–13.61, = 0.001). ASXL1 which displayed striking cardiac death (HR: 3.14; 1.24–7.93; 0.05) consistent associations observed subgroup 4.51; 1.30–15.6; 0.05). (iv) PCSK9 Tet2-CHIP both (correlation 0.1215, 0.011) overall enrolled 0.0578, 0.0382). (v) Bidirectional studies that development increases propensity CHIP. However, does not subsequently accelerate onset T2DM. mutations, particularly TET2, more prevalent without diabetes. these is adverse outcomes, notably increased rates. Moreover, analyses provide supporting evidence TET2-related Central Illustration: (T2DM): as demonstrated prospective Asian (AMI). predictive value marker poor prognosis has been assessed this study. suggest may increase CHIP, findings consortium. mellitus; haematopoiesis potential.
Язык: Английский
Процитировано
1
HemaSphere, Год журнала: 2023, Номер 7(10), С. e957 - e957
Опубликована: Окт. 1, 2023
Recent evidence revealed important interactions between clonal hematopoiesis (CH) and cellular therapies established for the treatment of hematologic malignancies. The impact CH on safety, efficacy, outcome chimeric antigen receptor (CAR) T-cell therapy is currently under investigation. We analyzed 110 patients with relapsed/refractory B-cell non-Hodgkin lymphoma (n = 105) or acute lymphoblastic leukemia (ALL) 5), treated Axicabtagene-Ciloleucel (39%), Tisagenlecleucel (51%), Brexucabtagene autoleucel (10%). Using error-corrected targeted sequencing, a high prevalence 56.4% (variant allele frequency [VAF] ≥1%) at time CAR infusion was detected. most frequently mutated gene PPM1D followed by DNMT3A, TET2, ASXL1, TP53. Variant frequencies were significantly lower in B T cells compared monocytes granulocytes. did not increase risk T-related toxicities. incidences cytokine release syndrome immune effector-cell-associated neurotoxicity similar CHpos CHneg patients, regardless clone size, age, product. Prolonged cytopenias associated CH. Best overall response rates (ORRs) numerically but higher (ORR 76.7% versus 62.2%; P 0.13). Furthermore, status predict progression-free survival survival. Lastly, sequential analysis showed modest VAF 1.3% acquisition novel mutations within 100 days postinfusion. frequent large lymphoma/ALL receiving T-cells affect toxicity nor outcome.
Язык: Английский
Процитировано
21
Journal of the American Heart Association, Год журнала: 2023, Номер 12(15)
Опубликована: Июль 25, 2023
ABSTRACT Clonal hematopoiesis of indeterminate potential (CHIP) is a common bone marrow abnormality induced by age‐related DNA mutations, which give rise to proinflammatory immune cells. These cells exacerbate atherosclerotic cardiovascular disease and may induce or accelerate heart failure. The mechanisms involved are complex but point toward central role for macrophages an inflammasome‐dependent response (IL‐1 [interleukin‐1] IL‐6 [interleukin‐6]) in the plaque directly myocardium. Intracardiac inflammation decrease cardiac function fibrosis, even absence disease. pathophysiology consequences CHIP differ among implicated genes as well subgroups patients with failure, based on cause (ischemic versus nonischemic) ejection fraction (reduced preserved fraction). Evidence accumulating that associated mortality ischemic nonischemic failure reduced development fraction. corresponding inflammatory pathways provide highly potent therapeutic target. Randomized controlled trials well‐phenotyped where readily available anti‐inflammatory therapies used intervene clonal hematopoiesis, pave way new area treatment. first clinical target already registered.
Язык: Английский
Процитировано
20
Neurology, Год журнала: 2024, Номер 102(4)
Опубликована: Янв. 31, 2024
Little is known about the role of radon in epidemiology stroke among women. We therefore examined association between home exposure and risk middle-aged older women United States. conducted a prospective cohort study postmenopausal aged 50-79 years at baseline (1993-1998) Women's Health Initiative. measured exposures as 2-day, indoor, lowest living-level average concentrations picocuries per liter (pCi/L) estimated 1993 by US Geological Survey reviewed Association American State Geologists under Indoor Radon Abatement Act. used Cox proportional hazards models to estimate incident, neurologist-adjudicated during follow-up through 2020 hazard ratio 95% CI, adjusting for design participant demographic, social, behavioral, clinical characteristics. Among 158,910 without (mean age 63.2 years; 83% white), 6,979 incident strokes were identified over 13.4 years). Incidence rates 333, 343, 349 100,000 woman-years <2, 2-4, >4 pCi/L, respectively. Compared with living <2 those 2-4 pCi/L had higher covariate-adjusted risks stroke: (95% CI) 1.06 (0.99-1.13) 1.14 (1.05-1.22). Using nonlinear spline functions model radon, was significantly elevated ranging from 2 4 (p = 0.0004), that is, below States Environmental Protection Agency Action Level mitigation (4 pCi/L). Associations slightly stronger ischemic (especially cardioembolic, small vessel occlusive, large artery atherosclerotic) than hemorrhagic stroke, but otherwise robust sensitivity analyses. associated moderately increased States, suggesting promulgation lower may help reduce domestic impact cerebrovascular disease on public health.
Язык: Английский
Процитировано
6
GeroScience, Год журнала: 2024, Номер 46(5), С. 5171 - 5189
Опубликована: Март 15, 2024
Язык: Английский
Процитировано
6
Leukemia, Год журнала: 2024, Номер 38(6), С. 1378 - 1389
Опубликована: Апрель 18, 2024
Clonal hematopoiesis (CH) driven by mutations in the DNA damage response (DDR) pathway is frequent patients with cancer and associated a higher risk of therapy-related myeloid neoplasms (t-MNs). Here, we analyzed 423 serial whole blood plasma samples from 103 relapsed high-grade ovarian receiving carboplatin, poly(ADP-ribose) polymerase inhibitor (PARPi) heat shock protein 90 (HSP90i) treatment within phase II EUDARIO trial using error-corrected sequencing 72 genes. DDR-driven CH was detected 35% longer duration prior PARPi treatment. TP53- PPM1D-mutated clones exhibited substantially clonal expansion rates than DNMT3A- or TET2-mutated during Expansion DDR correlated HSP90i exposure across three study arms partially abrogated presence germline related to homologous recombination deficiency. Single-cell selected revealed exclusivity mutations, identified DDR-mutated as origin t-MN two investigated cases. Together, these results provide unique insights into architecture preferential selection hematopoietic under intense DNA-damaging Specifically, therapies pose an independent for DDR-CH dose-dependent manner.
Язык: Английский
Процитировано
6
Nature Reviews Nephrology, Год журнала: 2023, Номер 20(3), С. 161 - 174
Опубликована: Окт. 26, 2023
Язык: Английский
Процитировано
15