THE J. BENJAMIN
ECKENHOFF FUND FOR RESEARCH IN HEMATOLOGY
Leukemia is a cancer of the blood and bone marrow that is often fatal within
months if left untreated. Even with aggressive treatment, including high
dose chemotherapy and bone marrow transplantation, five-year overall
survival rates for acute myeloid leukemia (AML) range between 30-40%. A
growing body of evidence indicates that not all cells in AML are the same.
Among leukemia cells, there is a rare population of cancer stem cells that
are ultimately responsible for maintaining the disease. These findings have
led to the idea that in order to cure this cancer, the leukemia stem cells
must be eliminated, while at the same time sparing normal blood forming stem
cells within the bone marrow. Dr. Ravi Majeti, Assistant Professor of
Hematology in Stanford's Institute for Stem Cell Biology and Regenerative
Medicine, is studying how to accomplish this.
The overall goal of his research is to identify molecular and genetic differences between AML stem cells and their normal blood forming counterparts, and then to develop therapeutic strategies directed against the cancerous stem cells. The Majeti lab has identified genes and pathways preferentially expressed or activated in leukemia stem cells. This analysis led to the identification of a number of proteins on the surface of leukemia stem cells that are more highly expressed in AML stem cells as compared to normal stem cells. They determined that one of these protein markers, CD47, contributes to leukemia development by blocking the ingestion and removal of leukemia cells by the body's natural immune system. Most significantly, they determined that blocking monoclonal antibodies directed against CD47 targeted leukemia stem cells significantly depleted leukemia in laboratory models.
The next major emphasis in Dr. Majeti's research is the development of therapeutic antibodies directed against CD47 and/or other proteins present in larger amounts on the external surface of leukemia stem cells compared to those present on normal blood forming stem cells. The ultimate goal is to develop a clinical grade therapeutic antibody for the treatment of AML that will be investigated in human clinical trials at the Stanford Cancer Center. Concurrently, Dr. Majeti and his colleagues are expanding their laboratory efforts to study other types of leukemia, including chronic lymphocytic leukemia, in the hopes of identifying similarly effective targets for therapy.
