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

Authors
Publication Date
Keywords
  • Cancer
  • Diseases & Disorders
  • Apoptosis
  • Cell Functions
  • Cell Types And Functions
  • Leukemia
  • Cancer Types
Disciplines
  • Biology
  • Medicine
  • Pharmacology

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.

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