Manumycin Induces Apoptosis of Leukemic Stem Cells Through Down-Regulation of Bcl2

Abstract 4738

Acute myeloid leukemia (AML) is a serious and often lethal hematopoietic malignant disease arising from stem cells. LSCs play the central role in the relapse and refractory of AML and highlight the critical need for the new therapeutic strategies to directly target the LSC population for ultimately curing leukemia. Unfortunately, very few agents have been shown to directly target the LSC population. The present studies demonstrate that manumycin, a farnesyltransferase inhibitor, resulted in viability decrease in a dose-dependent and soft agar clonogenic formation inhibition in LSCs isolated from KG1a cell line. Furthermore, manumycin induces LSC apoptosis in a dose-dependent. The molecular mechanism of manumycin mediated apoptosis is associated with down regulation of Bcl2 and Bcl-xL. In conclusion, manumycin triggers apoptosis in LSC and represents a potentially important new class of drugs for LSC-targeted therapy.