更新于：2024-05-01

CCUS Clonal Cytopenia of Undetermined Significance

意义不明的克隆性血细胞减少症

更新于：2024-05-01

基本信息

别名

CCUS、CCUS Clonal Cytopenia of Undetermined Significance、Clonal Cytopenia of Undetermined Significance

+ [1]

简介

Clinically meaningful cytopenia in one or more hematopoietic cell lineages. Clonal hematopoiesis is present with the variant allele frequency (VAF) equal or more that 2 percent. There is no other evidence of hematologic malignancy.

关联

项与意义不明的克隆性血细胞减少症相关的临床试验

NCT06240754 / Not yet recruiting临床2期IIT

A Pilot Study of Enasidenib for Patients With Clonal Cytopenia of Undetermined Significance and Mutations in IDH2: A Decentralized Trial

Study researchers think that a drug called enasidenib may help people with clonal cytopenia of undetermined significance (CCUS) because the drug blocks the mutated IDH2 protein, which may improve blood cell counts. The purpose of this study is to find out whether enasidenib is a safe and effective treatment for CCUS.

开始日期2024-04-30

申办/合作机构

Washington University School of Medicine

[+2]

NCT06063486 / Recruiting临床2期IIT

A Phase 2, Double-blind, Randomized Study to Compare the Effect of Curcumin Versus Placebo on Inflammatory Cytokines, Symptoms and Disease Parameters in Clonal Cytopenia of Undetermined Significance (CCUS), Low-Risk Myelodysplastic Syndrome (LR-MDS), and Myeloproliferative Neoplasms (MPNs)

This phase II trial evaluates how a curcumin supplement (C3 complex/Bioperine) changes the inflammatory response and symptomatology in patients with clonal cytopenia of undetermined significance (CCUS), low risk myelodysplastic syndrome (LR-MDS), and myeloproliferative neoplasms (MPN). Chronic inflammation drives disease development and contributes to symptoms experienced by patients with CCUS, LR-MDS, and MPN. Curcumin has been shown to have anti-inflammatory and anti-cancer properties and has been studied in various chronic illnesses and hematologic diseases.

开始日期2024-03-01

申办/合作机构

University of Southern California

[+1]

NCT05483010 / Recruiting临床2期IIT

Pilot Study of Statins in Patients With Clonal Cytopenia of Undetermined Significance (CCUS) and Myelodysplastic Syndromes (MDS)

Patients with clonal cytopenia of undetermined significance (CCUS) and lower-risk myelodysplastic syndromes (MDS) have a life expectancy of 5 to 10 years. Mortality in these patients results from progression of disease to higher-risk MDS or acute myeloid leukemia (AML) and cardiovascular events. Currently there are no FDA-approved treatments with the potential to improve survival of patients with CCUS and lower-risk MDS. Statins are an appealing class of drugs to consider in this situation as preclinical data support their potential to suppress progression of myeloid malignancy, and they have a well-established role in prevention of major cardiovascular events. This is a pilot study to explore the role of statins in treatment of patients with CCUS and lower-risk MDS. In this study, change in inflammatory biomarkers and variant allele frequency (VAF) of somatic mutations will be used as a surrogate marker of response to statin therapy. The hypothesis is that the use of statins at diagnosis of CCUS or lower-risk MDS will reduce inflammation and delay or prevent the expected increase in the VAF of somatic mutations over time.

开始日期2024-02-19

申办/合作机构

Washington University School of Medicine

100 项与意义不明的克隆性血细胞减少症相关的临床结果

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100 项与意义不明的克隆性血细胞减少症相关的转化医学

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0 项与意义不明的克隆性血细胞减少症相关的专利（医药）

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179

项与意义不明的克隆性血细胞减少症相关的文献（医药）

2024-02-15·Circulation

Clonal Hematopoiesis of Indeterminate Potential With Loss of Tet2 Enhances Risk for Atrial Fibrillation Through Nlrp3 Inflammasome Activation.

Article

作者: Amy Erica Lin ; Aneesh C Bapat ; Ling Xiao ; Abhishek Niroula ; Jianchuan Ye ; Waihay J Wong ; Mridul Agrawal ; Christopher J Farady ; Andreas Boettcher ; Christopher B Hergott ; Marie McConkey ; Patricio Flores-Bringas ; Veronica Shkolnik ; Alexander G Bick ; David Milan ; Pradeep Natarajan ; Peter Libby ; Patrick T Ellinor ; Benjamin L Ebert

BACKGROUND:

Clonal hematopoiesis of indeterminate potential (CHIP), a common age-associated phenomenon, associates with increased risk of both hematological malignancy and cardiovascular disease. Although CHIP is known to increase the risk of myocardial infarction and heart failure, the influence of CHIP in cardiac arrhythmias, such as atrial fibrillation (AF), is less explored.

METHODS:

CHIP prevalence was determined in the UK Biobank, and incident AF analysis was stratified by CHIP status and clone size using Cox proportional hazard models. Lethally irradiated mice were transplanted with hematopoietic-specific loss of Tet2, hematopoietic-specific loss of Tet2 and Nlrp3, or wild-type control and fed a Western diet, compounded with or without NLRP3 (NLR [NACHT, LRR {leucine rich repeat}] family pyrin domain containing protein 3) inhibitor, NP3-361, for 6 to 9 weeks. Mice underwent in vivo invasive electrophysiology studies and ex vivo optical mapping. Cardiomyocytes from Ldlr^-/- mice with hematopoietic-specific loss of Tet2 or wild-type control and fed a Western diet were isolated to evaluate calcium signaling dynamics and analysis. Cocultures of pluripotent stem cell-derived atrial cardiomyocytes were incubated with Tet2-deficient bone marrow-derived macrophages, wild-type control, or cytokines IL-1β (interleukin 1β) or IL-6 (interleukin 6).

RESULTS:

Analysis of the UK Biobank showed individuals with CHIP, in particular TET2 CHIP, have increased incident AF. Hematopoietic-specific inactivation of Tet2 increases AF propensity in atherogenic and nonatherogenic mouse models and is associated with increased Nlrp3 expression and CaMKII (Ca2+/calmodulin-dependent protein kinase II) activation, with AF susceptibility prevented by inactivation of Nlrp3. Cardiomyocytes isolated from Ldlr^-/- mice with hematopoietic inactivation of Tet2 and fed a Western diet have impaired calcium release from the sarcoplasmic reticulum into the cytosol, contributing to atria arrhythmogenesis. Abnormal sarcoplasmic reticulum calcium release was recapitulated in cocultures of cardiomyocytes with the addition of Tet2-deficient macrophages or cytokines IL-1β or IL-6.

CONCLUSIONS:

We identified a modest association between CHIP, particularly TET2 CHIP, and incident AF in the UK Biobank population. In a mouse model of AF resulting from hematopoietic-specific inactivation of Tet2, we propose altered calcium handling as an arrhythmogenic mechanism, dependent on Nlrp3 inflammasome activation. Our data are in keeping with previous studies of CHIP in cardiovascular disease, and further studies into the therapeutic potential of NLRP3 inhibition for individuals with TET2 CHIP may be warranted.

2024-02-06·Tuberculosis and respiratory diseases

Clonal hematopoiesis of indeterminate potential is associated with current smoking status and history of exacerbation in patients with COPD.

Article

作者: Jung-Kyu Lee ; Hongyul An ; Youngil Koh ; Chang-Hoon Lee

Background:

There is limited data regarding the clinical outcomes of clonal hematopoiesis of indeterminate potential (CHIP) in patients with chronic obstructive pulmonary disease (COPD). This study aimed to evaluate the clinical significance of CHIP as a COPD biomarker.

Methods:

This retrospective study was conducted on patients with COPD who were enrolled prospectively in the Seoul National University Hospital Airway Registry from January 2013 to December 2019 and underwent pulmonary function and blood tests. We evaluated the CHIP score according to smoking status and severity of airflow obstruction.

Results:

We analyzed next-generation sequencing data to detect CHIP in 125 patients with COPD. Current smokers had a higher prevalence of CHIP in DTP, DNMT3A, and PPM1D genes than in never- or ex-smokers. CHIP of DTP and DNMT3A genes was significantly associated with current smokers (aOR 2.80, 95% CI 1.01-7.79; aOR 4.03, 95% CI 1.09-14.0). Patients with moderate-to-severe airflow obstruction had a higher prevalence of CHIP in most of the explored genes than those with mild obstruction, although the difference was not statistically significant. CHIP in ASXL1 genes was significantly associated with history of mild, severe, and total acute exacerbation.

Conclusion:

Given that CHIP in specific genes was significantly associated with current smoking status and acute exacerbation, CHIP can be considered as a candidate biomarker for COPD patients.

2024-01-19·iScience

Mechanism and anti-corrosion measures of carbon dioxide corrosion in CCUS: A review

Review

作者: Yan, Ting ; Xu, Liang-Chen ; Zeng, Zhuo-Xiong ; Pan, Wei-Guo

Carbon capture, utilization, and storage (CCUS) technology is widely recognized as a key solution for mitigating global climate change. Consequently, it has received significant attention from countries worldwide. However, carbon dioxide corrosion poses a significant challenge to CCUS and represents a bottleneck to the large-scale development and application of this technology. To mitigate this issue, this review starts with a discussion of corrosion problems in CCUS. Later, the fundamentals of the carbon dioxide corrosion mechanism are introduced. Then, the influences of various factors that affect the corrosion are highlighted, such as water content, pH, flow rate, etc. Afterward, we summarize the commonly used methods for corrosion protection, with a particular focus on inhibitor, given their eco-friendly and effective nature. Lastly, challenges and prospects are discussed to motivate future studies on developing novel, high-performance green inhibitor and studying the corresponding protection mechanisms, hoping to make some contributions to carbon emission reduction.