Identifying the phenotypic and genetic markers of Clonal Haematopoiesis of Indeterminate Potential (CHIP)
As we age, our blood system can become damaged which then increases our chance of developing blood cancers, such as leukaemia. We currently do not understand which patients will develop blood cancers, and when and how they develop them, meaning that we cannot provide treatment. In addition, detecting people with damaged blood cells is currently expensive, making clinical management difficult. Our ultimate aim is to identify vulnerabilities in diseased cells that can be detected early, before cancer occurs, and can be detected and targeted with therapeutics to improve health and minimise the development of cancer.
Clonal haematopoiesis of indeterminate potential (CHIP), affects 10% of the population older than 65 years and has been linked with an increase in cardiovascular and haematological malignancies. However, current methods of detection fall short and make treatment difficult. Whilst some of the key genetic drivers of CHIP have been well characterised, we still lack a comprehensive understanding of its pathogenesis: using the UK BioBank, we will characterise CHIP and then utilise this rich phenotypic resource to try to assess for other drivers that might precipitate its onset. Including:
1) Characterise the presence of Clonal Haematopoiesis of Indeterminate Potential (CHIP) in the UK Bio-Bank. Using a panel of known CHIP somatic variants, we aim to assess the allelic fractions of each variant - orthologous to the scale of the clonal expansion - and fully characterise the presence of this phenomenon in the population.
2) Assess for novel and co-occurring somatic and germline genetic lesions
3) We will utilise the breadth of available phenotypic data to conduct a comprehensive understanding of the phenotypic drivers of CHIP