Discovery of novel therapy for cancers with PTPN11 mutations

One of the worst genetic changes that causes leukaemia is mutation in a gene called PTPN11. Our research team is developing a method to understand how it works using primary blood stem cells and screening small molecules.

Unusually, PTPN11 mutations can somehow cause cancer without needing help from other mutations.

We are beginning to enter a new age of precision medicine based on the molecular profile for each cancer at the time of diagnosis. One of the most common and least understood molecular alterations is mutation in the tyrosine phosphatase PTPN11. This causes the worst prognosis myeloid leukaemia in children, called juvenile myelomonocytic leukaemia.

This team has developed sophisticated methods to target human blood stem cells to mimic common mutations in cancer and sophisticated assays that reveal the pro-tumorigenic properties of these mutations. The team has also developed methods at SAHMRI to measure signalling changes in small numbers of stem cells using TIMS-TOF mass spectrometry. These tools will be used to discover mutation-specific inhibitory molecules for cancer treatments.

This project is funded by CSL Limited, the National Health and Medical Research Council and the National Institutes of Health