Grant: Operating Grant

Chronic myelogenous Leukemia (CML) is a form of blood cancer that affects the bone marrow and later on the spleen and the liver. In this disease, malignantly transformed blood cells grow in an uncontrolled manner and displace the normal blood cells and this interferes with the body's immune defense and oxygen transport. Currently, CML can be treated with a drug called Imatinib (Glevec), which eliminates the majority of the leukemic cells. However, the malignantly transformed leukemia stem cells remain intact under this treatment and foster a re-emergence of the disease, when Imatinib is discontinued or when a resistance has developed. We have described two transcription factors called Gfi1 and Gfi1b that are essential for the function of stem cells in the bone marrow. These stem cells are able to form all blood cells that are found in our body. Intriguingly these bone marrow stem cells are the same cells that are affected in CML, where they become malignantly transformed, loose their ability to produce the specialized blood cells and multiply in an uncontrolled manner. The present proposal investigates whether a deletion of the Gfi1 or Gfi1b genes, either each individually or both together, can kill the CML leukemic stem cells and can complement the current treatment that is available for CML to cure this disease.