Role of the DNA damage checkpoint response in pre-leukaemic cells predisposed to AML

Principal Investigator: Dr Philip Zegerman, Gurdon Institute/Department of Biochemistry
Funded by: CRUK Cambridge Centre Early Detection Programme Pump Priming Awards 2020

The clinical utility of ATR, CHK1, and WEE1 inhibitors, especially as single agents, will likely depend on identifying and targeting cancers that are dependent on DNA damage checkpoint activation. This study analysing checkpoint function during the development of AML will provide novel understanding of the role of checkpoint activation during the evolution of leukaemogenesis. This work has the potential to identify the DNA damage checkpoint as an early stage biomarker to assess AML disease outcome and inform therapy choices.

Brian Huntly is the scientific deputy director of the UK National Cancer Research Institute (NCRI) AML working group and he is currently setting up a clinic in Cambridge Universities Hospitals (CUH) for patients with AML-associated mutations but no current haematological disorder (a condition known as Clonal Haemopoiesis of Indeterminate Potential or CHIP). This line-of-sight to the clinic will facilitate the early translation of any therapeutic findings of this award. Similarly, if checkpoint activation is identified as an early event in experimental premalignancy then this will be checked in patient samples with myeloid pre-leukaemias and correlated with outcomes such as an increased risk of the development of AML.