University Health Network
In Vivo Studies of Acute Myeloid Leukemia and its Hypoxia Status within the Bone Marrow Microenvironment
Acute myeloid leukemia (AML) is a disease of the bone marrow (BM) that spreads throughout the BM of affected patients. The BM microenvironment supports the development of leukemic cells, and typically the BM is hypoxic (low oxygen). In solid tumours, hypoxia is associated with poor prognosis and resistance to therapy. Since leukemia is not considered a solid tumour, the influence of a hypoxic microenvironment on disease progression has not been adequately studied. Moreover, the study of hypoxia in hematological diseases, like AML, has been slowed by the lack of reliable experimental methods. Recent studies have shown that hypoxia influences leukemic cell proliferation, differentiation, maintenance and resistance to chemotherapy. Despite recognizing that the importance of the hypoxic BM microenvironment in developing new treatment strategies, much of past and current research has been carried out in suspension cultures or in histological sections which fail to replicate the patient setting and only tell us what is happening at a fixed period in time. Drs. Ralph DaCosta and Mark Minden's teams at the Princess Margaret Cancer Centre, for the first time, will apply state-of-the-art optical imaging methods in animal models of AML to visualize AML cells and their complex behaviors in the hypoxic BM microenvironment in real-time and at the single cell level. Findings from this research will improve our understanding of how AML cells grow in the BM which could lead to new treatments for this disease. The experimental tools developed in this unique bench-to-bedside collaboration will also open up new avenues for basic research in leukemia which could help overcome previous technological barriers in the field.