Cincinnati Children's researchers publish findings on potential target for leukemia treatment

Study discovering a critical role of RhoH GTPase in the development and activation of white blood cells published in Nature Immunology

Cincinnati Children's Hospital Medical Center today announced the publication of pioneering research identifying the crucial role and novel mechanism of action of the protein RhoH GTPase in the development and activation of cells critical to the immune system. The findings, along with other studies, suggest that RhoH GTPase may provide a target for therapeutic intervention in some types of leukemia. The paper is due to appear in an upcoming edition of the journal Nature Immunology and was recently posted in the advance online publication section of the journal's website, (www.nature.com/ni/index.html).

The paper describes detailed genetic and biochemical studies undertaken by researchers in the Division of Experimental Hematology and the Division of Immunobiology. The investigators succeeded in identifying a crucial role for RhoH GTPase in the development of thymocytes and activation of T-lymphocytes, both key processes in immune cell development. In addition, the researchers uncovered a novel mechanism for regulating RhoH activity, which may have broad implications in improving researchers' understanding of the mechanism of action of the Rho GTPase protein family and provide a potential target for leukemia drug development.

"We continue to make important progress in deciphering the molecular processes involved in the development and maintenance of the immune and blood system and how disruption of key proteins may contribute to leukemia," said David A Williams, M.D., Director of Experimental Hematology, Cincinnati Children's. "Through a collaboration with Ohio State University Comprehensive Cancer Center, we are now focused on translating these findings into developing new ways to target the protein as a novel approach to treating hematological malignancy."

The development of mature white blood cells, including lymphocytes, is a highly complex process involving cell growth as well as specific genetic and biochemical steps. Disruption of this process is associated with diseases such as leukemia.

RhoH GTPase is specific to blood-forming cells. Experiments have shown that its alteration affects several key steps in the growth and development of white blood cells. Moreover, clinical samples have implicated RhoH GTPase as a factor in leukemia and lymphoma. Further work is ongoing to decipher the specific mechanism of regulation and the function of RhoH GTPase in the development of white blood cell populations.

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Cincinnati Children's Hospital Medical Center, one of the leading pediatric research institutions in the nation, is dedicated to changing the outcome for children throughout the world. Cincinnati Children's ranks second among all pediatric institutions in the United States in grants from the National Institutes of Health. It has an established tradition of research excellence, with discoveries including the Sabin oral polio vaccine, the surfactant preparation that saves the lives of thousands of premature infants each year, and a rotavirus vaccine that saves the lives of hundreds of thousands of infants around the world each year. Current research directions include the translation of basic laboratory research into the development of novel therapeutics for the treatment of disease, and furthering the development of personalized and predictive medicine.


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