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

SP Glaser, EF Lee, E Trounson, P Bouillet… - Genes & …, 2012 - genesdev.cshlp.org
SP Glaser, EF Lee, E Trounson, P Bouillet, A Wei, WD Fairlie, DJ Izon, J Zuber
Genes & development, 2012genesdev.cshlp.org
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-xL and
Mcl-1. Here we report that removal of Mcl-1, but not loss or pharmacological blockade of Bcl-
xL, 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 …
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-xL and Mcl-1. Here we report that removal of Mcl-1, but not loss or pharmacological blockade of Bcl-xL, 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.
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