Anti-apoptotic mcl-1 is essential for the development and sustained growth of acute myeloid leukemia Academic Article uri icon

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.

authors

  • Glaser, SP
  • Lee, EF
  • Trounson, E
  • Bouillet, P
  • Wei, A
  • Fairlie, WD
  • Izon, DJ
  • Zuber, J
  • Rappaport, AR
  • Herold, MJ
  • Alexander, WS
  • Lowe, SW
  • Robb, L
  • Strasser, A

publication date

  • 2012

has subject area