July 2, 2012 Researchers at the University of Cincinnati Hoxworth Blood Center have discovered a new gene target for leukemia therapy.
These findings, slated for the July 26, 2012 print issue of Blood, the journal of the American Society of Hematology, could lead to cellular targets for a patient population that otherwise may not have desirable outcomes and could potentially stop the onset of leukemia before it begins.
A team led by Jose Cancelas, MD, PhD, an associate professor of pediatrics at the UC College of Medicine and director of the research division at Hoxworth Blood Center, found that by inhibiting in animal models the protein Vav3, which controls cell signaling, the development of this leukemia -- known as BCR-ABL lymphoid leukemia -- is delayed.
"Despite advances in the treatment of this disease, the outcome of patients with this type of leukemia is very poor because it develops resistance to standard therapies," he says. "We found that the genetic deficiency of Vav3 delays the formation of leukemia by impairing the signals from BCR-ABL and the overproduction of leukemic cells. In doing this, it also allows the standardized therapies, or BCR-ABL inhibitors, to work."
Cancelas says this finding could lead to new multi-targeted therapies where Vav3 activity is related to the formation of leukemia.
"In collaboration with Dr. Nicolas Nassar, associate professor of pediatrics at UC and a physician in the division of experimental hematology at Cincinnati Children's Hospital Medical Center, we are now trying to find chemicals with Vav3 inhibitory activity," he says. "With this knowledge, we may be able to develop a therapy that can greatly improve the lives of patients facing leukemia."
Other authors of this multinational study are Kyung Hee Chang and Susan Dunn from Hoxworth Blood Center; and Yi Zheng, John Perentesis, Abel Sanchez-Aguilera, Amitava Sengupta, Malav Madhu, Ashley Ficker, Rebecca Santho and Ashley Kuenzi from Cincinnati Children's. Collaborators also include David Williams (Boston Children's Hospital, Harvard Medical School), Michael Deininger (University of Utah), Xose Bustelo (University of Salamanca, Spain) and Xabier Agirre (University of Navarra, Spain).
This study was funded by the National Heart, Lung and Blood Institute of the National Institutes of Health, the United States Department of Defense, Alex's Lemonade Stand Foundation and Cancer Free Kids Foundation.
Continuation of this study has been recently funded by the Leukemia and Lymphoma Society of North America.
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- K. H. Chang, A. Sanchez-Aguilera, S. Shen, A. Sengupta, M. N. Madhu, A. M. Ficker, S. K. Dunn, A. M. Kuenzi, J. L. Arnett, R. A. Santho, X. Agirre, J. P. Perentesis, M. W. Deininger, Y. Zheng, X. R. Bustelo, D. A. Williams, J. A. Cancelas. Vav3 collaborates with p190-BCR-ABL in lymphoid progenitor leukemogenesis, proliferation and survival. Blood, 2012; DOI: 10.1182/blood-2011-06-361709
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