Maintaining the proper balance of white cell production in the bone marrow requires a complex interplay between stem and early progenitor cells and the microenvironment. A lack of regulation of this process can result in blood diseases, including myelodysplasia and acute myelogenous leukemia (AML). These diseases can occur across the age span from young infancy to old age.
The laboratory of Vivienne Rebel has been studying the role of CREB binding protein (CREBBP) and its role in maintaining normal white cell production in the bone marrow. Mice which are lacking one copy of the CREBBP gene demonstrate not only abnormal white cell production, resulting in the development of myelodysplasia and in some cases AML, but in addition display a decrease in bone volume within the bone marrow, thereby altering the environment of the white cell production. Learn
In humans, the loss of 1 copy of CREBBP is associated with Rubinstein-Taybi Syndrome, associated with multiple congenital anomalies and an increased risk to develop cancer. Moreover, mutations in the CREBBP gene have been found in lung, ovarian, and esophageal cancer and most recently in acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma.