Campuses:

Chronic Myelogenous Leukemia: a Disease Caused by Abnormal Adhesion of Stem Cells to the Marrow Microenvironment

Wednesday, November 18, 1998 - 2:00pm - 3:00pm
Keller 3-180
Catherine Verfaillie (University of Minnesota, Twin Cities)
Normal blood production takes place in close contact with the marrow microenvironment. Adhesion receptors, such as beta-1-integrins anchor blood progenitors to extracellular matrix components such as fibronectin. Further, adhesion through beta-1-integrins transfers signals that inhibit blood progenitor growth.

Chronic Myelogenous Leukemia (CML) is a lethal leukemia that is characterized by an abnormal, premature circulation of blood progenitors in the blood and continuous progenitor proliferation. The abnormal circulation and proliferation of CML progenitors can at least in part be explained by the inability of beta-1-integrins on CML progenitors to adhere to fibronectin and to transfer signals that inhibit blood progenitor growth. CML is caused by the rearrangement between two genes, called BCR and ABL. The resulting novel oncogene, BCR/ABL generates a oncoprotein that is responsible for the defect in beta-1-integrin mediated adhesion and signaling: treatment of CML blood progenitors with antisense oligonucleotides against BCR/ABL which eliminate the oncoprotein restores adhesion and adhesion mediated signaling.

Understanding the mechanism(s) causing the defective beta1-integrin-function in CML, which is partly responsible for the abnormal circulation and growth of CML progenitors, may lead to the discovery of novel agents that restore normal regulation of CML progenitor growth and trafficking, and induce remission.