Theodoros Karantanos, MD, PhD

Secondary acute myeloid leukemia (sAML) is a blood cancer that develops in patients with previous bone marrow diseases. Unfortunately, sAML patients have poor survival and limited therapies. It is urgently needed to discover new drugs that can kill leukemia cells in these patients. We found that a molecule called CCRL2, located in the surface of normal cells, is elevated in sAML cells. CCRL2 increases the growth of these cells and renders them resistant to a widely used treatment for sAML called azacitidine. We found that CCRL2 activates inflammation inside leukemia cells, which may contribute to their growth. We also found that certain drugs can kill at a much higher-level sAML cells having CCRL2 in their surface compared to cells that do not have it. Our first goal is to discover exactly how CCRL2 activates inflammation in sAML. We will utilize microscopy and protein analysis from sAML cells and use specific drug inhibitors. Our second goal is to understand if activation of inflammation indeed contributes to sAML growth. We will edit leukemia cells genes and study mice that carry these cells. Our last goal is to analyze drugs that kill leukemia cells with CCRL2 in their surface when combined with the available therapies for this disease. Our work can lead to the discovery a new mechanism that promotes the growth of leukemia cells in sAML patients and introduce new therapies that have the potential to prolong the survival of patients with this devastating disease.