Targeting glycolysis in leukemia: A novel inhibitor 3-BrOP in combination with rapamycin

Lauren J. Akers; Wendy Fang; Alejandro G. Levy; Anna R. Franklin; Peng Huang; Patrick A. Zweidler-McKay

doi:10.1016/j.leukres.2010.12.028

Targeting glycolysis in leukemia: A novel inhibitor 3-BrOP in combination with rapamycin

Lauren J. Akers, Wendy Fang, Alejandro G. Levy, Anna R. Franklin, Peng Huang, Patrick A. Zweidler-McKay

Research output: Contribution to journal › Article › peer-review

41 Scopus citations

Abstract

Rapidly proliferating solid tumor cells are often dependent on glycolysis for ATP production even in normoxia (the Warburg effect), however it is not yet clear whether acute leukemias have a similarly increased dependence on aerobic glycolysis. We report that all acute leukemia subtypes (pre-B ALL, T-ALL and AML) demonstrated growth arrest and cell death when treated the novel glycolysis inhibitor 3-BrOP. Potentiated ATP depletion and pro-apoptotic effects were seen for 3-BrOP combinations with the cytochrome-c-reductase inhibitor antimycin A and the mTOR inhibitor rapamycin. These results reveal a potential role for glycolysis inhibition in acute leukemia subtypes and suggest potential combinations.

Original language	English (US)
Pages (from-to)	814-820
Number of pages	7
Journal	Leukemia Research
Volume	35
Issue number	6
DOIs	https://doi.org/10.1016/j.leukres.2010.12.028
State	Published - Jun 2011

Keywords

ALL
AML
ATP
MTOR

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

MD Anderson CCSG core facilities

Flow Cytometry and Cellular Imaging Facility

Access to Document

10.1016/j.leukres.2010.12.028

Cite this

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title = "Targeting glycolysis in leukemia: A novel inhibitor 3-BrOP in combination with rapamycin",

abstract = "Rapidly proliferating solid tumor cells are often dependent on glycolysis for ATP production even in normoxia (the Warburg effect), however it is not yet clear whether acute leukemias have a similarly increased dependence on aerobic glycolysis. We report that all acute leukemia subtypes (pre-B ALL, T-ALL and AML) demonstrated growth arrest and cell death when treated the novel glycolysis inhibitor 3-BrOP. Potentiated ATP depletion and pro-apoptotic effects were seen for 3-BrOP combinations with the cytochrome-c-reductase inhibitor antimycin A and the mTOR inhibitor rapamycin. These results reveal a potential role for glycolysis inhibition in acute leukemia subtypes and suggest potential combinations.",

keywords = "ALL, AML, ATP, MTOR",

author = "Akers, {Lauren J.} and Wendy Fang and Levy, {Alejandro G.} and Franklin, {Anna R.} and Peng Huang and Zweidler-McKay, {Patrick A.}",

note = "Funding Information: These studies were supported through UT M.D. Anderson Cancer Center Startup Funds. No grant or commercial interest was involved. ",

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AU - Akers, Lauren J.

AU - Fang, Wendy

AU - Levy, Alejandro G.

AU - Franklin, Anna R.

AU - Huang, Peng

AU - Zweidler-McKay, Patrick A.

N1 - Funding Information: These studies were supported through UT M.D. Anderson Cancer Center Startup Funds. No grant or commercial interest was involved.

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AB - Rapidly proliferating solid tumor cells are often dependent on glycolysis for ATP production even in normoxia (the Warburg effect), however it is not yet clear whether acute leukemias have a similarly increased dependence on aerobic glycolysis. We report that all acute leukemia subtypes (pre-B ALL, T-ALL and AML) demonstrated growth arrest and cell death when treated the novel glycolysis inhibitor 3-BrOP. Potentiated ATP depletion and pro-apoptotic effects were seen for 3-BrOP combinations with the cytochrome-c-reductase inhibitor antimycin A and the mTOR inhibitor rapamycin. These results reveal a potential role for glycolysis inhibition in acute leukemia subtypes and suggest potential combinations.

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KW - AML

KW - ATP

KW - MTOR

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Targeting glycolysis in leukemia: A novel inhibitor 3-BrOP in combination with rapamycin

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

Access to Document

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