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Updated: Jun 27, 2026

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation
Published on: May 3, 2024
Acute myeloid leukemia-targeted toxin activates both apoptotic and necroptotic death mechanisms
Henrick Horita1, Arthur E Frankel, Andrew Thorburn
1Department of Pharmacology, University of Colorado Denver School of Medicine, Aurora, Colorado, United States of America.
Background:
Acute myelogenous leukemia (AML) is the second most common leukemia with approximately 13,410 new cases and 8,990 deaths annually in the United States. A novel fusion toxin treatment, diphtheria toxin GM-CSF (DT-GMCSF) has been shown to selectively eliminate leukemic repopulating cells that are critical for the formation of AML. We previously showed that DT-GMCSF treatment of U937 cells, an AML cell line, causes activation of caspases and the induction of apoptosis.
Methods And Findings:
In this study we further investigate the mechanisms of cell death induced by DT-GMCSF and show that, in addition to the activation of caspase-dependent apoptosis, DT-GMCSF also kills AML cells by simultaneously activating caspase-independent necroptosis. These mechanisms depend on the ability of the targeted toxin to inhibit protein synthesis, and are not affected by the receptor that is targeted or the mechanism through which protein synthesis is blocked.
Conclusions:
We conclude that fusion toxin proteins may be effective for treating AML cells whether or not they are defective in apoptosis.
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