What Are The Roles Of MEIS1, BMI1 And HOXB Genes In Self-Renewal Of Acute Myeloid Leukaemia Stem Cells? (360G-Wellcome-211023_Z_18_Z)

Acute myeloid leukaemia (AML) is the commonest aggressive leukaemia in adults. Due to treatment resistance and relapse, the prognosis for most patients is poor. In normal blood cell development, stem cells are the most immature cells and can produce any type of blood cell. AML results when bone marrow cells acquire genetic alterations, called mutations. These mutations occur in early bone marrow cells and result in a ‘leukaemic stem cell’, which maintains growth of the leukaemia. Previous work in the Vyas laboratory has identified genes that are switched on in AML patients that cause leukemic stem cells to grow abnormally, including HOX genes. This project aims to further our understanding of the impact of these genes in leukaemic stem cells by answering questions such as: Is AML cell growth impaired when these genes are switched off? Do leukaemia cells behave like normal blood cells when these genes are switched off? Does switching on the genes make normal bone marrow cells behave like leukaemia cells? What mechanisms allow these genes to regulate the function of leukaemia cells? Our overall aim is to use this information to design treatment strategies to eradicate leukaemic stem cells.