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Wang Z, Mi T, Bradley HL, et al. Pimozide and Imipramine Blue Exploit Mitochondrial Vulnerabilities and Reactive Oxygen Species to Cooperatively Target High Risk Acute Myeloid Leukemia. Antioxidants (Basel). 2021;10(6)doi: 10.3390/antiox10060956.
Wang, Z., Mi, T., Bradley, H. L., Metts, J., Sabnis, H., Zhu, W., Arbiser, J., & Bunting, K. D. (2021). Pimozide and Imipramine Blue Exploit Mitochondrial Vulnerabilities and Reactive Oxygen Species to Cooperatively Target High Risk Acute Myeloid Leukemia. Antioxidants (Basel, Switzerland), 10(6), . https://doi.org/10.3390/antiox10060956
Wang, Zhengqi, et al. "Pimozide and Imipramine Blue Exploit Mitochondrial Vulnerabilities and Reactive Oxygen Species to Cooperatively Target High Risk Acute Myeloid Leukemia." Antioxidants (Basel, Switzerland) vol. 10,6 (2021). doi: https://doi.org/10.3390/antiox10060956
Wang Z, Mi T, Bradley HL, Metts J, Sabnis H, Zhu W, Arbiser J, Bunting KD. Pimozide and Imipramine Blue Exploit Mitochondrial Vulnerabilities and Reactive Oxygen Species to Cooperatively Target High Risk Acute Myeloid Leukemia. Antioxidants (Basel). 2021 Jun 15;10(6). doi: 10.3390/antiox10060956. PMID: 34203664; PMCID: PMC8232307.
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Antioxidants (Basel). 2021 Jun 15;10(6). doi: 10.3390/antiox10060956.

Pimozide and Imipramine Blue Exploit Mitochondrial Vulnerabilities and Reactive Oxygen Species to Cooperatively Target High Risk Acute Myeloid Leukemia.

Antioxidants (Basel, Switzerland)

Zhengqi Wang, Tian Mi, Heath L Bradley, Jonathan Metts, Himalee Sabnis, Wandi Zhu, Jack Arbiser, Kevin D Bunting

Affiliations

  1. Division of Hem/Onc/BMT, Department of Pediatrics, Emory University, Atlanta, GA 30322, USA.
  2. Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, School of Medicine, Emory University, Atlanta, GA 30322, USA.
  3. Department of Dermatology, Emory University, Atlanta, GA 30322, USA.
  4. Veterans Administration Medical Center, Atlanta, GA 30322, USA.

PMID: 34203664 PMCID: PMC8232307 DOI: 10.3390/antiox10060956

Abstract

Acute myeloid leukemia (AML) is a heterogeneous disease with a high relapse rate. Cytokine receptor targeted therapies are therapeutically attractive but are subject to resistance-conferring mutations. Likewise, targeting downstream signaling pathways has been difficult. Recent success in the development of synergistic combinations has provided new hope for refractory AML patients. While generally not efficacious as monotherapy, BH3 mimetics are very effective in combination with chemotherapy agents. With this in mind, we further explored novel BH3 mimetic drug combinations and showed that pimozide cooperates with mTOR inhibitors and BH3 mimetics in AML cells. The three-drug combination was able to reach cells that were not as responsive to single or double drug combinations. In Flt3-internal tandem duplication (ITD)-positive cells, we previously showed pimozide to be highly effective when combined with imipramine blue (IB). Here, we show that Flt3-ITD

Keywords: BH3 mimetic; Flt3-internal tandem duplication; acute myeloid leukemia; mTOR inhibitor; mitoSox; reactive oxygen species; repurposed drugs

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