Last update 01 Nov 2024

CCUS Clonal Cytopenia of Undetermined Significance

Last update 01 Nov 2024

Basic Info

Synonyms

CCUS, CCUS Clonal Cytopenia of Undetermined Significance, Clonal Cytopenia of Undetermined Significance

+ [3]

Introduction

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.

Drugs associated with CCUS Clonal Cytopenia of Undetermined Significance

Olutasidenib

Target

IDH1

Mechanism

IDH1 inhibitors

Active Org.

FORMA Therapeutics, Inc. [+2]

Originator Org.

Forma Therapeutics Holdings, Inc.

Active Indication

IDH1 Mutation Acute Myeloid Leukemia [+15]

Inactive Indication

Advanced Malignant Solid Neoplasm [+5]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date01 Dec 2022

Enasidenib Mesylate

Target

IDH2

Mechanism

IDH2 inhibitors

Active Org.

Celgene Corp. [+5]

Originator Org.

Celgene Corp.

Active Indication

Acute Myeloid Leukemia [+11]

Inactive Indication

Advanced Malignant Solid Neoplasm [+5]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date01 Aug 2017

Clinical Trials associated with CCUS Clonal Cytopenia of Undetermined Significance

NCT06566742 / Not yet recruitingPhase 2IIT

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.

Start Date28 Feb 2025

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+1]

NCT06240754 / RecruitingPhase 2IIT

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.

Start Date10 Oct 2024

Sponsor / Collaborator

Washington University School of Medicine

[+2]

NCT06063486 / RecruitingPhase 2IIT

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.

Start Date01 Mar 2024

Sponsor / Collaborator

University of Southern California

[+1]

100 Clinical Results associated with CCUS Clonal Cytopenia of Undetermined Significance

100 Translational Medicine associated with CCUS Clonal Cytopenia of Undetermined Significance

0 Patents (Medical) associated with CCUS Clonal Cytopenia of Undetermined Significance

215

Literatures (Medical) associated with CCUS Clonal Cytopenia of Undetermined Significance

01 Nov 2024·Metabolism

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

Review

Author: 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.

01 Oct 2024·Hepatology

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

Article

Author: 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.

01 Oct 2024·The Journal of Molecular Diagnostics

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

Article

Author: 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.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

CCUS Clonal Cytopenia of Undetermined Significance

Basic Info

Related

Analysis