更新于：2024-11-01

CCUS Clonal Cytopenia of Undetermined Significance

意义不明的克隆性血细胞减少症

更新于：2024-11-01

基本信息

别名

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

+ [3]

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药物

Olutasidenib

靶点

IDH1

作用机制

IDH1抑制剂

在研机构

FORMA Therapeutics, Inc. [+2]

原研机构

Forma Therapeutics Holdings, Inc.

在研适应症

IDH1突变急性髓性白血病 [+15]

非在研适应症

晚期恶性实体瘤 [+5]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2022-12-01

Enasidenib Mesylate

甲磺酸恩西地平

靶点

IDH2

作用机制

IDH2抑制剂

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2017-08-01

项与意义不明的克隆性血细胞减少症相关的临床试验

NCT06566742 / Not yet recruiting临床2期IIT

A Phase 2 Study Evaluating Olutasidenib in Patients With IDH1-mutated Clonal Cytopenia of Undetermined Significance and Lower-risk Myelodysplastic/Syndromes/Chronic Myelomonocytic Leukemia.

To learn if olutasidenib can help to control CCUS, MDS, and/or CMML. The safety of the drug will also be studied.

开始日期2025-02-28

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

NCT06240754 / 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2024-10-10

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]

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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215

项与意义不明的克隆性血细胞减少症相关的文献（医药）

2024-11-01·Metabolism

Steatotic liver disease in the context of hematological malignancies and anti-neoplastic chemotherapy

Review

作者: Pontikoglou, Charalampos G ; Filippatos, Theodosios D ; Matheakakis, Angelos ; Papadaki, Helen A

The rising prevalence of obesity-related illnesses, such as metabolic steatotic liver disease (MASLD), represents a significant global public health concern. This disease affects approximately 30 % of the adult population and is the result of metabolic abnormalities rather than alcohol consumption. Additionally, MASLD is associated with an increased risk of cardiovascular disease (CVD), chronic liver disease, and a variety of cancers, particularly gastrointestinal cancers. Clonal hematopoiesis (CH) is a biological state characterized by the expansion of a population of blood cells derived from a single mutated hematopoietic stem cell. The presence of CH in the absence of a diagnosed blood disorder or cytopenia is known as clonal hematopoiesis of indeterminate potential (CHIP), which itself increases the risk of hematological malignancies and CVD. Steatotic liver disease may also complicate the clinical course of cancer patients receiving antineoplastic agents, a condition referred to as chemotherapy induced steatohepatitis (CASH). This review will present an outline of the various aspects of MASLD, including complications. Furthermore, it will summarize the existing knowledge on the emerging association between CHIP and MASLD and present the available data on patient cases with concurrent MASLD and hematological neoplasms. Finally, it will provide a brief overview of the chemotherapeutic drugs associated with CASH, the underlying pathophysiologic mechanisms and their clinical implications.

2024-10-01·Hepatology

Impact of clonal hematopoiesis of indeterminate potential on hepatocellular carcinoma in individuals with steatotic liver disease

Article

作者: Dongiovanni, Paola ; Pelusi, Serena ; Reeves, Helen L. ; Malvestiti, Francesco ; Miele, Luca ; Federico, Alessandro ; Bolli, Niccolò ; Moretti, Vittoria ; McCain, Misti V. ; La Mura, Vincenzo ; Marchetti, Alfredo ; Ricchiuti, Antony ; Vespasiani-Gentilucci, Umberto ; D’Ambrosio, Roberta ; Ronzoni, Luisa ; Prati, Daniele ; Soardo, Giorgio ; Lionetti, Marta ; Marella, Alessio ; Valenti, Luca ; Bugianesi, Elisabetta

Background and Aims:Metabolic dysfunction–associated steatotic liver disease (MASLD) is a global epidemic and is the most rapidly rising cause of HCC. Clonal hematopoiesis of indeterminate potential (CHIP) contributes to neoplastic and cardiometabolic disorders and is considered a harbinger of tissue inflammation. CHIP was recently associated with increased risk of liver disease. The aim of this study was to examine whether CHIP is associated with HCC development in patients with SLD.Approach and Results:We considered individuals with MASLD-HCC (n=208) and controls with (n =414) and without (n =259) advanced fibrosis who underwent whole exome sequencing. CHIP was diagnosed when ≥2 variant callers identified a known myeloid mutation with variant allele frequency ≥2%. CHIP was observed in 116 participants (13.1%), most frequently in DNMT3A, TET2, TP53, and ASXL1, and correlated with age (p<0.0001) and advanced liver fibrosis (p=0.001). Higher aspartate aminotransferase levels predicted non-DNMT3A-CHIP, in particular with variant allele frequency ≥10% (OR: 1.14, 1.03 −1.28 and OR: 1.30, 1.12 −1.49, respectively, p<0.05). After adjustment for sex, diabetes, and a polygenic risk, a score of inherited MASLD predisposition CHIP was associated with cirrhosis (2.00, 1.30 −3.15, p=0.02), and with HCC even after further adjustment for cirrhosis (OR: 1.81, 1.11 −2.00, 1.30 −3.15, p=0.002). Despite the strong collinearity among aging and development of CHIP and HCC, non-DNTM3A-CHIP, and TET2 lesions remained associated with HCC after full correction for clinical/genetics covariates and age (OR: 2.45, 1.35 −4.53; OR: 4.8, 1.60 -17.0, p=0.02).Conclusions:We observed an independent association between CHIP, particularly related to non-DNTM3A and TET2 genetic lesions and MASLD-HCC.

2024-10-01·The Journal of Molecular Diagnostics

Detection and Interpretation of Clonal Hematopoiesis Variants during Routine Solid Tumor Next-Generation Sequencing

Article

作者: Jennings, Lawrence J ; Vormittag-Nocito, Erica R. ; Gao, Juehua ; Nocito, Kevin L. ; Nocito, Kevin L ; Sukhanova, Madina ; Vormittag-Nocito, Erica R ; Menon, Adil ; Jennings, Lawrence J.

Clonal hematopoiesis (CH) and clonal cytopenia of undetermined significance (CCUS) are recently recognized diagnostic entities that serve as an independent risk factors for cardiovascular disease and myeloid malignancy. CH is an incidental finding, and evaluation of the incidence of CH/CCUS-associated mutations in solid tumor next-generation sequencing samples was undertaken to better understand the prevalence of mutations in this population. A retrospective review of clinical sequencing data for solid tumor malignancies diagnosed between February 2022 and April 2023 on next-generation sequencing data was performed. Cases were reviewed for variants in genes associated with CH/CCUS. Variant allele frequencies and other factors of the sequencing data were assessed for determining risk of CH/CCUS. A total of 2479 cases were evaluated during the study period. Of these, 29 cases demonstrated potential CH/CCUS-associated mutations, with a total of 33 variants identified. These were identified in a variety of tumor types, with gliomas being the most common. Significant cardiac histories were found in over half of cases identified, and few cases had abnormal blood counts. Detailed criteria for flagging variants as suspicious for CH and recommendations for these criteria as future guidelines for reporting are described. These variants are incidental findings that require more extensive follow-up or change in therapy management using a single institutional cohort.