Clonal Hematopoiesis

This study will investigate the association between clonal hematopoiesis and other conditions. Clonal hematopoiesis (CH) refers to the mutations in a person's stem cells which commonly affect people as they get older. These mutations have notably been linked to increased risk of certain cancers as well as increased risk of heart disease.

Clonal hematopoiesis (CH), including clonal hematopoiesis of indeterminate potential (CHIP), is an age-associated condition characterized by the expansion of hematopoietic stem and progenitor cell clones carrying acquired somatic mutations. Although CH is associated with an increased risk of hematologic malignancies, its greater public health impact derives from its strong association with cardiovascular diseases, including coronary artery disease and stroke. Emerging evidence suggests that CH-associated mutations promote chronic inflammatory signaling in myeloid immune cells, thereby contributing to atherosclerosis and adverse cardiovascular remodeling. This observational translational study aims to characterize the biological spectrum of clonal hematopoiesis across different stages of disease risk and manifestation. Using state-of-the-art single-cell and multi-omics approaches, the study will compare inflammatory pathways, immune cell states, and mutation-associated molecular programs among healthy individuals without CH, individuals with high-risk CH, and patients with CH-associated hematologic or cardiovascular disease. The ultimate goal is to identify shared and disease-specific mechanisms linking clonal hematopoiesis to adverse clinical outcomes and to generate insights for future preventive, anti-clonal, and anti-inflammatory therapeutic strategies.

This study assesses how blood cell growth patterns (clonal hematopoiesis) relate to heart health or cardiovascular disease (CVD) after treatment in patients with Hodgkin lymphoma. In some patients, cancer treatment at a young age may lead to later complications, including problems with heart health. Checking for blood cell growth patterns called therapy-related clonal hematopoiesis (t-CH) can help predict who might be at risk for heart health problems after Hodgkin lymphoma treatment. If doctors know who may be at greater risk for developing later heart complications, then they can more closely monitor those patients to prevent or detect heart complications early.

The researchers are doing this study to find out whether a high-fiber plant-based diet (HFPBD) can improve quality of life for people with CH. A HFPBD includes foods that are mainly from plants (for example, fruits,vegetables, nuts, beans, and whole grains). The researchers will measure quality of life by having participants complete questionnaires/surveys.

People identified to have CH or thought to have possible CH due to unexplained low blood cell counts, including low red blood cells, white blood cells, or platelets will be asked to take part in the study. Individuals who are confirmed to have CH and provide informed consent to participate in the study will have monitoring of their CH, assessment of the risk of heart diseases, blood cancers and personalised support. The researchers will also measure people's understanding of CH and how they feel after learning about CH. Researchers will then record the relevant information from people with CH in a central database over time to track long-term health outcomes. The information collected from the study will help create a blueprint for doctors to provide care for people with CH in the future, and guide further research into CH in Australia. Participants will be asked to donate blood samples for the study for research purposes including CH monitoring and testing and also provide health information for the central database.

This study is being done to investigate clonal hematopoiesis and therapy-emergent myeloid neoplasms in patients with ovarian or other solid cancers. Researchers want to identify risk factors for developing these blood cancers as well as if there is/are a genetic/environmental component(s) to developing blood cancer.

The purpose of this research study is to learn more about variants in the TP53 gene both associated with Li-Fraumeni Syndrome (LFS), a hereditary cancer risk condition, and TP53 variants found in the blood for other reasons (e.g. ACE/CHIP and mosaicism).

Clonal hematopoiesis (CH) is characterized by the overproduction of blood cells derived from a single hematopoietic stem and progenitor cell (HSPC) harboring certain somatic mutations. It is linked to serious outcomes, including cardiovascular disease, myeloid neoplasm (MN), and increased mortality. Clonal Cytopenia of Uncertain Significance (CCUS) is a CH subtype characterized by associated persistent cytopenia. It affects approximately 10 % of people over 70 and is the most advanced precursor state with the highest risk of progressing to MN. There is an unmet need to determine whether modifying CH can prevent adverse outcomes. Current blood cancer therapies are too toxic for precursor conditions like CH. MOSAIC is a randomized double-blind placebo-controlled trial that will test a novel low-dose oral epigenetic therapy-decitabine with tetrahydrouridine (Dec+THU) in CCUS. It has shown targeted, non-cytotoxic reversal of common CH mutations in preclinical and early-phase studies. The goal is to develop a safe and effective therapy in CCUS that restores normal blood cell production and prevents progression.

Current data on the impact of donor CHIP on long-term recipient outcome remain largely speculative. Data on the impact of donor CHIP including on allograft function, immunologic dysfunction, graft versus host disease (GVHD), disease relapse and survival across various donor populations are scarce. This is a retrospective-prospective cohort study designed to determine the association between donor gene mutations and outcome following allogeneic HSCT.