Acute myeloid leukaemia (AML) is an aggressive and lethal blood cancer with a 5-year overall survival of less than 45% for patients younger than 60 years of age, or less than 10% for older patients. In Australia, about 1,000 patients are newly diagnosed with AML each year, and about 60,000 new AML patients per year are estimated for the developed world in total. Most patients initially respond to chemotherapy but ultimately relapse and die from disease. Relapse is mediated by leukaemia stem cells that initiate, maintain and serially propagate AML. The development of therapeutic strategies to target leukaemia stem cells is therefore a promising approach and key priority.
We have previously performed comprehensive, randomised, Phase II – like preclinical trials in humanised AML models treated with standard induction chemotherapy and/or novel telomerase inhibition therapy. Using extensive mutational and transcriptional profiling techniques, we have identified molecular biomarker candidates for resistance and response to therapy. The aim of this project is to characterise biomarker candidates using CRISPR/Cas9 technology in AML models. This project is not limited to but will involve cell culture techniques, molecular biology, immunoblotting, and flow cytometry.
Bruedigam C, Bagger FO, Heidel FH, Paine Kuhn C, Guignes S, Song A, Austin R, Vu T, Lee E, Riyat S, Moore AS, Lock RB, Bullinger L, Hill GR, Armstrong SA, Williams DA, Lane SW. Telomerase inhibition effectively targets mouse and human AML stem cells and delays relapse following chemotherapy. Cell Stem Cell 2014.
Bruedigam C, Lane SW. Telomerase in hematologic malignancies. Curr Opin Hematol 2016.
Bruedigam C, Wackrow B, Song A, Porter AH, Lee S, Moore AS, Abdel-Wahab O, Lane SW. The preclinical efficacy of a novel telomerase inhibitor, imetelstat, in AML-a randomized trial in patient-derived xenografts. Blood 2016. Cited 1 time.
Bruedigam C, Porter AH, Wackrow B, Straube J, Cooper LT, Song A, Lee S, Abdel-Wahab O, Hill GR, Lane SW. Integrated molecular analysis identifies replicative stress as sensitizer to imetelstat therapy in AML. Blood 2017.