• Study Reveals Achilles’ Heel of Lymphoid Leukemia

    Discovering what they call the “Achilles’ heel” for lymphoid leukemia, an international research team reports early success with an experimental treatment that eradicated the disease in “humanized” mice.

    The study found that inhibiting a protein called Gfi1 caused leukemic cells to die in mice bred to accept human cancer cells. If the treatment can be shown to work in humans, this new molecular therapy could make acute lymphoid leukemia (ALL) much more susceptible to chemotherapy and radiation treatments.

    The study, led by researchers at Cincinnati Children’s and the Institut de recherches cliniques de Montreal (ICRM), was published Feb. 11, 2013, in the journal Cancer Cell

    “Chemo and radiation therapies are very non-specific and can be toxic to patients. Our findings suggest that combining the inhibition of Gfi1 with these treatments may allow the use of lower cytotoxic doses and directly benefit patients,” says H. Leighton Grimes, PhD, co-senior investigator on the study and a researcher in the divisions of Cellular and Molecular Immunology and Experimental Hematology at Cincinnati Children’s.

    Also collaborating was co-senior investigator, Tarik Möröy, PhD, president and scientific director of the ICRM in Montreal.

    ALL is the most common type of leukemia in children, according to the Leukemia and Lymphoma Society of America.  The disease occurs most often in the first decade of life but increases in frequency again in older individuals. More effective treatment could reduce the toxic side effects of current therapies and help prevent remission, the researchers say.

    In healthy people, a protein called p53 represses tumor formation by triggering programmed cell death. But in people with ALL, the cancer cells use the Gfi1 protein – which has an important role in forming normal lymphoid cells -- to override p53’s tumor repressing capabilities.  

    When the researchers removed Gfi1 in mouse lymphoid tumors in culture, the leukemia regressed.  Next, the research team inserted T-cell leukemia cells from human patients into mice. Inhibiting Gfi1 in the mice stopped the cancer progression without any harmful effects.  The team is working to determine if these results will be translatable to human patients.

    Collaborators on the study included co-first authors, James Phelan, PhD, now a postdoctoral fellow at the National Cancer Institute, and Cyrus Khandanpour, MD, now with the University Hospital of the University of Duisburg-Essen in Germany.

    Read more about Grimes’ research in the latest issue of Research Horizons.

  • H. Leighton Grimes, PhD, is the co-senior investigator on the study.

    H. Leighton Grimes, PhD, is the co-senior investigator on the study.