Dr Wendy Parker and Dr David Yeung
Supported by Light the Night ‘Shooting Star’ 2013, Sharon Cox
Chief investigators: Dr Wendy Parker and Dr David Yeung
Institute: SA Pathology
Project title: Developing novel methods to examinedrug
resistance in chronic myeloid leukaemia
Disease focus: Chronic myeloid leukaemia (CML)
Funding period: 2014
Up to a third of patients with chronic myeloid leukaemia (CML) develop resistance to the front-line treatment, tyrosine kinase inhibitor (TKI), imatinib. It appears that CML cells ‘escape’ destruction from the drug by acquiring single or multiple mutations in the BCRABL1 gene.
Using a sensitive new analysis, Dr Wendy Parker and Dr David Yeung found up to a quarter of patients resistant to imatinib had low-level BCR-ABL1 gene mutations. They also showed more than a quarter of patients had two or more BCR-ABL1 gene mutations after developing imatinib resistance.
To understand which BCR-ABL1 mutations lead to drug resistance, the pair is developing a test to accurately identify the different types of mutations. They then will correlate the mutations found in CML patients with treatment outcomes.
According to Dr Parker, an accurate understanding of the mechanisms leading to resistance to TKI drugs (including imatinib and the more recent dasatinib, nilotinib and ponatinib) is critical.
“Chronic myeloid leukaemia patients are experiencing treatment failure because we don’t fully understand drug resistance in this cancer,” she said.
“By defining the BCR-ABL1 mutations associated with resistance, and creating an accurate and sensitive prognostic test for these mutations, clinicians will have a vital tool to guide their selection of the best therapy for patients who would otherwise fail treatment.”
Dr Parker was awarded the 2013 Leukaemia Foundation of Australia/Cure CancerAustralia Post doctoral Research Fellowship.