Mechanisms of Age-Related Clonal Haemopoiesis

Research summary

The primary objective is to identify blood and/or bone marrow samples from adults with CHIP and evaluate the mechanisms by which mutations confer a competitive advantage to blood stem and progenitor cells. This includes determining where mutations occur in the cellular hierarchy of blood production,assessing their functional consequences,and analysing their effects on gene expression through RNA-sequencing and epigenetic analysis. Secondary objectives include measuring cell division and differentiation rates in normal human haematopoiesis,evaluating how these dynamics change during aging,and examining correlations between the biological characteristics of mutant clones and subsequent evolution in clonal size. Methodologically,the study involves collecting blood and/or bone marrow samples from adults undergoing planned orthopaedic surgery,particularly total hip replacement and knee surgery. Bone marrow will be obtained from the femur during hip replacement surgery,utilizing tissue that would otherwise be discarded. Blood samples will be collected from both hip replacement patients and an independent cohort undergoing knee surgery. Next-generation genetic sequencing will be used to identify samples with CHIP. For participants with CHIP who consent to follow-up,subsequent blood samples will be collected to monitor changes in mutant clone size over time.

Principal Investigator

Mr Antony Palmer

Contact us

Email: christopher.deane@ouh.nhs.uk

IRAS number

231756