Could have applications to other forms of cancer
University of Nebraska Medical Center researchers have engineered a mouse model that will allow scientists to better study the origin and regulation of cancer stem cells in leukemia.
The research was reported in the Aug. 30 issue of the Proceedings of the National Academy of Sciences, a leading science journal.
The study was carried out by a UNMC Eppley Cancer Center team headed by Hamid Band, M.D., Ph.D., professor and associate director of translational research, and Mayumi Naramura, M.D., assistant professor, in collaboration with Vimla Band, Ph.D., professor and chairwoman, department of genetics, cell biology and anatomy.
The new mouse model will provide key new insights into a form of leukemia caused by defective Cbl genes. Dr. Band and other scientists have been studying Cbl genes since the 1990s.
Recent clinical studies by a number of groups, including collaborative studies by Dr. Band with Martin Sattler, Ph.D., at the Dana-Farber Cancer Institute in Boston, have shown that mutations in Cbl genes cause human leukemias, which often are seen in very young children that inherit a defective Cbl gene from an apparently healthy parent.
How these gene defects produce leukemia is a key to designing targeted therapies for these patients. The new mouse model opens the door to studies of basic mechanisms of how hematopoietic stem cells are controlled and how defects in Cbl genes or their targets produce human leukemia.
The model should also facilitate discovery of agents to treat cancer patients with defective Cbl genes, Dr. Band said. Such agents also could help turn off normal Cbl genes to facilitate expansion of hematopoietic stem cells for use in transplantation medicine, Dr. Naramura said.
Since stem cells serve as the cells of origin for essentially all human cancers and are responsible for tumor recurrence and resistance, Drs. Band and Naramura said the animal model is likely to shed crucial light on other cancers in addition to leukemia.
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