INDUCTION OF APOPTOSIS IN MULTIDRUG-RESISTANT AND RADIATION-RESISTANTACUTE MYELOID-LEUKEMIA CELLS BY A RECOMBINANT FUSION TOXIN DIRECTED AGAINST THE HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR-RECEPTOR

Multiagent chemotherapy regimens fail to cure more than one-half of th e patients with acute myeloid leukemia (AML) because of the emergence of dominant multidrug-resistant subclones of leukemia cells, We have d eveloped a recombinant diphtheria toxin-human granulocyte macrophage c olony-stimulating factor chimeric fusion protein (DT(ct)GMCSF) that sp ecifically targets GMCSF receptor-positive AML cells, This novel bioth erapeutic agent induced rapid apoptotic cell death of chemotherapy-res istant AML cell lines and primary leukemic cells from treatment-refrac tory AML patients. Our results suggest that DT(ct)GMCSF mag be useful in the treatment of AML patients whose leukemia has recurred and devel oped resistance to contemporary chemotherapy programs.