Leukaemias, the cancers of the blood, arise via the accumulation of genetic lesions that subvert normal cellular regulation and result in unrestrained proliferation. Understanding the genetic landscape that defines leukemia – the variation in disease causing lesions and the interactions between accumulated mutations – will provide powerful insights into how disease arises and progresses, and create new opportunities for improved leukemia diagnosis and treatment. Our current studies include application of genomics and genetics tools to define genetic lesions driving specific leukaemias, with particular focus on disease progression, the evolution to more malignant disease, and the genetic changes influencing response to therapy.