Investigating immune cell “macrophage” driven drug resistance in Acute Myeloid Leukaemia

Resistance to cancer drugs ( therapy resistance) is one of the main contributing factors towards poor survival in Acute Myeloid Leukaemia (AML); the second most common leukaemia in adults and children. Cross-talk between AML cells, and bone marrow (BM) dwelling cells, significantly contributes towards therapy resistance. Potential cancer-supporting macrophages (immune cells) are elevated in the BM of blood acute myeloid leukaemia patients and other blood cancer patients, and have been shown to play a role in therapy resistance. Our initial findings from our collaborative studies suggest that substances released from macrophages can protect AML cells from traditional and new targeted cancer drugs. We also show that protection mediated by macrophages is associated with upregulation of the STAT3-ERK1/2-MCL-1 cell survival pathway. We predict that by targeting this pathway, via clinically applicable inhibitors obtained from our collaborators, that we can overcome bone marrow mediated therapy resistance in AML. To interrogate this, my lab will investigate the ability of AML cell released factors in re-educating macrophages to a leukaemia- supportive type, and in turn ascertain the impact of these macrophages on therapy resistance in AML. In the long-term these studies will lead to the development of much needed new drugs to safely and effectively treat, and improve AML patient survival.