The polarity protein, Par3, is a member of the partitioning defective (Par) polarity complex and consists of three PSD-95/Dlg/ZO-1 (PDZ) protein binding domains and a self-homologous binding region. The latter allows Par3 to form large complexes, hence Par3 is often referred to as the master polarity regulator. As a scaffolding protein, Par3 interacts with different intracellular transcriptional pathways which are frequently deregulated in cancer. These include the MAPK/ERK, JAK/STAT and Tiam1/Rac pathways. In addition, Par3 can also bind PIPs and PTEN through its PDZ2 and PDZ3 binding domains respectively and is thus hypothesised to regulate the PI3K/AKT pathway. Par3 acts in a context dependent manner as either a tumour promoter or suppressor in multiple human epithelial cancers, including breast, skin and renal cell carcinomas. However, the role of polarity proteins in haematopoietic malignancies is largely unknown. We are investigating the effect of Par3 loss in haematopoiesis and leukaemogenesis utilising two different mouse models, Mx1-Cre and hScl-Cre, to conditionally delete Par3 and/or Pten. We have confirmed deletion of Pten results in acute myeloid leukaemia (AML)/T cell acute lymphocytic leukaemia (T-ALL) and represents an excellent preclinical model for studying these malignancies. Using multiple techniques, we show that Par3 is expressed in all haematopoietic organs and at every stage of haematopoietic development from the stem cells and progenitors to the differentiated progeny. An extensive multicolour flow cytometry regime reveals loss of Par3 together with loss of Pten exacerbates the onset of AML/T-ALL and results in a significant increase in the proportion and number of granulocyte/macrophage progenitors (GMPs) and Pre-pro B cells. Importantly, the GMP stage of development is critical for the progression of AML, suggesting Par3 predisposes mice to the development of AML.