Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia

Stefan P Glaser; Erinna F Lee; Evelyn Trounson; Phillipe Bouillet; Andrew Wei; W Douglas Fairlie; David J Izon; Johannes Zuber; Amy R Rappaport; Marco Herold; Warren S Alexander; Scott W Lowe; Lorraine M Robb; Andreas Strasser

doi:10.1101/gad.182980.111

Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia

Stefan P Glaser, Erinna F Lee, Evelyn Trounson, Phillipe Bouillet, Andrew Wei, W Douglas Fairlie, David J Izon, Johannes Zuber, Amy R Rappaport, Marco Herold, Warren S Alexander, Scott W Lowe, Lorraine M Robb, Andreas Strasser

Australian Centre for Blood Diseases

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

357 Citations (Scopus)

Abstract

Acute myeloid leukemia (AML) frequently relapses after initial treatment. Drug resistance in AML has been attributed to high levels of the anti-apoptotic Bcl-2 family members Bcl-x L and Mcl-1. Here we report that removal of Mcl-1, but not loss or pharmacological blockade of Bcl-x L, Bcl-2, or Bcl-w, caused the death of transformed AML and could cure disease in AML-afflicted mice. Enforced expression of selective inhibitors of prosurvival Bcl-2 family members revealed that Mcl-1 is critical for survival of human AML cells. Thus, targeting of Mcl-1 or regulators of its expression may be a useful strategy for the treatment of AML. A? 2012 by Cold Spring Harbor Laboratory Press.

Original language	English
Pages (from-to)	120 - 125
Number of pages	6
Journal	Genes & Development
Volume	26
Issue number	2
DOIs	https://doi.org/10.1101/gad.182980.111
Publication status	Published - 2012

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Glaser, S. P., Lee, E. F., Trounson, E., Bouillet, P., Wei, A., Fairlie, W. D., Izon, D. J., Zuber, J., Rappaport, A. R., Herold, M., Alexander, W. S., Lowe, S. W., Robb, L. M., & Strasser, A. (2012). Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia. Genes & Development, 26(2), 120 - 125. https://doi.org/10.1101/gad.182980.111

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abstract = "Acute myeloid leukemia (AML) frequently relapses after initial treatment. Drug resistance in AML has been attributed to high levels of the anti-apoptotic Bcl-2 family members Bcl-x L and Mcl-1. Here we report that removal of Mcl-1, but not loss or pharmacological blockade of Bcl-x L, Bcl-2, or Bcl-w, caused the death of transformed AML and could cure disease in AML-afflicted mice. Enforced expression of selective inhibitors of prosurvival Bcl-2 family members revealed that Mcl-1 is critical for survival of human AML cells. Thus, targeting of Mcl-1 or regulators of its expression may be a useful strategy for the treatment of AML. A? 2012 by Cold Spring Harbor Laboratory Press.",

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AU - Glaser, Stefan P

AU - Lee, Erinna F

AU - Trounson, Evelyn

AU - Bouillet, Phillipe

AU - Wei, Andrew

AU - Fairlie, W Douglas

AU - Izon, David J

AU - Zuber, Johannes

AU - Rappaport, Amy R

AU - Herold, Marco

AU - Alexander, Warren S

AU - Lowe, Scott W

AU - Robb, Lorraine M

AU - Strasser, Andreas

PY - 2012

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AB - Acute myeloid leukemia (AML) frequently relapses after initial treatment. Drug resistance in AML has been attributed to high levels of the anti-apoptotic Bcl-2 family members Bcl-x L and Mcl-1. Here we report that removal of Mcl-1, but not loss or pharmacological blockade of Bcl-x L, Bcl-2, or Bcl-w, caused the death of transformed AML and could cure disease in AML-afflicted mice. Enforced expression of selective inhibitors of prosurvival Bcl-2 family members revealed that Mcl-1 is critical for survival of human AML cells. Thus, targeting of Mcl-1 or regulators of its expression may be a useful strategy for the treatment of AML. A? 2012 by Cold Spring Harbor Laboratory Press.

UR - http://genesdev.cshlp.org/content/26/2/120.full.pdf

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DO - 10.1101/gad.182980.111

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EP - 125

JO - Genes & Development

JF - Genes & Development

IS - 2

ER -

Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia

Abstract

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