Therapeutic vulnerabilities of TET2-mutant clonal haematopoiesis

Summary

Clonal haematopoiesis (CH), the clonal expansion of a haematopoietic stem cell (HSC) and its progeny driven by somatic mutations, is the shared pre-clinical ancestor of all types of myeloid malignancies (MM), including acute myeloid leukaemia (AML), myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). CH becomes increasingly common with age to affect >30% of people over 70yrs. 

Somatic mutations in the TET2 gene are the second most common cause of CH overall, and the most common cause amongst individuals aged 70 years or older (see figure).  CH driven by biallelic mutations in TET2 gene carries a high risk of progression to MM. 

Project aims

This project will investigate the pathogenesis and therapeutic vulnerabilities of TET2-mutant CH using mouse models, primary human cells from volunteers with this from of CH and genetically edited human stem cells cultured in vitro.

Main techniques to be used:
CRISPR screens, clonal competition studies, metabolomics, investigation of existing and novel therapeutics in vitro and in-vivo (mouse models)

Contact details

Professor George Vassiliou - gsv20@cam.ac.uk

Opportunities

This project is open to applicants who want to do a:

• PhD