KWF grant awarded to study the role of macrophages in AML

Acute myeloid leukemia (AML) is a disease that is still difficult to treat, with an unfavorable prognosis and average 5-year survival rates of 25%. Many patients initially do respond well to chemotherapy, but the disease often re-emerges over time as a consequence of remaining therapy-resistant cells that give rise to relapse of disease. AML is not solely composed of undifferentiated leukemic blasts in the bone marrow, but also of various tumor-associated cells such as stromal cells and innate and adaptive immune cells. While the exact role of such immune cells during leukemic transformation is only beginning to become revealed, more and more evidence pinpoints to their critical importance. In our preliminary studies we have identified that a subgroup of – in particular poor prognosis AML patients – contains a large proportion of so-called tumor supportive M2- type macrophages. For the first time we have begun to functionally study the role of these cells in AML and have shown that they indeed support leukemic growth in vitro and in vivo, and impose drug resistance. The overarching aim of the current proposal is to characterize the mechanisms by which M2-type macrophages support tumor growth, and develop tools to exploit these mechanisms as part of novel therapies.