(E,E)-bisantrene suppresses MYC expression and displays anti-leukemic activity in acute myeloid leukemia
- 1The University of Newcastle
Abstract
Background: Acute myeloid leukemia (AML) is genetically diverse with a high unmet clinical need for improved treatment options. Dysregulation of the transcription factor MYC plays a central role in AML progression and therapeutic resistance. (E,E)-bisantrene was recently found to inhibit MYC transcription and downstream activity via G-quadruplex DNA stabilization. This study aimed to evaluate the mechanism of action and preclinical activity of (E,E)-bisantrene in AML. Methods: The in vitro and in vivo activity of (E,E)-bisantrene was determined in a variety of AML models (cell lines, xenograft mouse models, and ex vivo human AML mononuclear cells). Transcriptomic, proteomic and phosphoproteomic analyses were performed after treatment with (E,E)-bisantrene. Analyses of -omics data to identify enriched pathways and upstream regulators were performed. Results: (E,E)-bisantrene demonstrated potent anti-proliferative activity across a panel of AML cell lines, inducing apoptosis and reducing S phase proportions. (E,E)-bisantrene significantly prolonged survival in cell- and patient-derived xenograft models of AML. Mechanistically, RNA-seq and proteomic analysis of MOLM13 and MV4-11 cells treated with (E,E)-bisantrene showed significant reductions in the activity of MYC and E2F, together with the cell cycle regulators CDK1/2/4/5. Transcript and protein levels of MYC were reduced in a dose- and time-dependent manner. TP53 and inflammation-associated transcript signatures were also observed. Conclusion: Anti-proliferative activity of (E,E)-bisantrene in preclinical AML models was associated with a downregulation of MYC, CDK1/2/4/5 and E2F. This study supports the ongoing clinical evaluation of (E,E)-bisantrene in AML where MYC is a clinically relevant driver of disease aggressiveness and therapy resistance.
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BibTeX
@misc{murray2026eebisantrene,
title = {{(E,E)-bisantrene suppresses MYC expression and displays anti-leukemic activity in acute myeloid leukemia}},
author = {H. C. Murray and K. Miller and J. Brzozowski and D. Kiltschewskij and I. Roy and N. Panicker and A. S. Woldu and B. J. Buckley and M. Messina and C. Penney and P. Cuthbertson and S. Sahni and D. Tillett and M. J. Kelso and J. Sillar and M. J. Cairns and A. Enjeti and N. M. Verrills},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.10.750805},
url = {https://www.biorxiv.org/content/10.64898/2026.09.10.750805v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - (E,E)-bisantrene suppresses MYC expression and displays anti-leukemic activity in acute myeloid leukemia
AU - H. C. Murray
AU - K. Miller
AU - J. Brzozowski
AU - D. Kiltschewskij
AU - I. Roy
AU - N. Panicker
AU - A. S. Woldu
AU - B. J. Buckley
AU - M. Messina
AU - C. Penney
AU - P. Cuthbertson
AU - S. Sahni
AU - D. Tillett
AU - M. J. Kelso
AU - J. Sillar
AU - M. J. Cairns
AU - A. Enjeti
AU - N. M. Verrills
PY - 2026
DA - 2026/09/10
PB - bioRxiv
DO - 10.64898/2026.09.10.750805
UR - https://www.biorxiv.org/content/10.64898/2026.09.10.750805v1
AB - Background: Acute myeloid leukemia (AML) is genetically diverse with a high unmet clinical need for improved treatment options. Dysregulation of the transcription factor MYC plays a central role in AML progression and therapeutic resistance. (E,E)-bisantrene was recently found to inhibit MYC transcription and downstream activity via G-quadruplex DNA stabilization. This study aimed to evaluate the mechanism of action and preclinical activity of (E,E)-bisantrene in AML. Methods: The in vitro and in vivo activity of (E,E)-bisantrene was determined in a variety of AML models (cell lines, xenograft mouse models, and ex vivo human AML mononuclear cells). Transcriptomic, proteomic and phosphoproteomic analyses were performed after treatment with (E,E)-bisantrene. Analyses of -omics data to identify enriched pathways and upstream regulators were performed. Results: (E,E)-bisantrene demonstrated potent anti-proliferative activity across a panel of AML cell lines, inducing apoptosis and reducing S phase proportions. (E,E)-bisantrene significantly prolonged survival in cell- and patient-derived xenograft models of AML. Mechanistically, RNA-seq and proteomic analysis of MOLM13 and MV4-11 cells treated with (E,E)-bisantrene showed significant reductions in the activity of MYC and E2F, together with the cell cycle regulators CDK1/2/4/5. Transcript and protein levels of MYC were reduced in a dose- and time-dependent manner. TP53 and inflammation-associated transcript signatures were also observed. Conclusion: Anti-proliferative activity of (E,E)-bisantrene in preclinical AML models was associated with a downregulation of MYC, CDK1/2/4/5 and E2F. This study supports the ongoing clinical evaluation of (E,E)-bisantrene in AML where MYC is a clinically relevant driver of disease aggressiveness and therapy resistance.
ER -