Acute myeloid leukaemia (AML) is the most common acute leukaemia in adults and is associated with a poor prognosis, largely due to the frequent emergence of treatment resistance. Although resistance is the leading cause of mortality, its underlying mechanisms remain poorly understood. Leukemic cells in AML are defined by a block in maturation along the blast differentiation trajectory, resulting in a distorted representation of normal haematopoietic development, underscoring the need to view AML as a dynamic disease. Malignant transformation and adaptive resistance may therefore arise at multiple positions along a heterogeneous differentiation landscape, rather than from a single static cellular state. Due to this high level of cellular heterogeneity in AML, investigation into disease mechanisms have been non-trivial. Here, we will investigate resistance mechanisms in AML using single-cell sequencing and various bulk sequencing approaches. Ultimately, this work seeks to enable more personalised treatment strategies and improve long-term outcomes for patients with AML.