Induction of apoptosis in multidrug-resistant and radiation-resistant acute myeloid leukemia cells by a recombinant fusion toxin directed against the human granulocyte macrophage colony-stimulating factor receptor.
basic_science · Level V
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Abstract
Multiagent chemotherapy regimens fail to cure more than one-half of the patients with acute myeloid leukemia (AML) because of the emergence of dominant multidrug-resistant subclones of leukemia cells. We have developed a recombinant diphtheria toxin-human granulocyte macrophage colony-stimulating factor chimeric fusion protein (DTctGMCSF) that specifically targets GMCSF receptor-positive AML cells. This novel biotherapeutic agent induced rapid apoptotic cell death of chemotherapy-resistant AML cell lines and primary leukemic cells from treatment-refractory AML patients. Our results suggest that DTctGMCSF may be useful in the treatment of AML patients whose leukemia has recurred and developed resistance to contemporary chemotherapy programs.
Medical subject headings
- Apoptosis
- Diphtheria Toxin
- Drug Resistance, Multiple
- Granulocyte-Macrophage Colony-Stimulating Factor
- Immunotoxins
- Radiation Tolerance
- Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
- Recombinant Fusion Proteins