Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia
Copyright policy )Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia
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.
- The Alfred Hospital Australia
- University of Melbourne Australia
- Monash University Australia
- Memorial Sloan Kettering Cancer Center United States
- Walter and Eliza Hall Institute of Medical Research Australia
Antineoplastic Agents, Hormonal, Cell Survival, Gene Expression Regulation, Neoplastic, Mice, Inbred C57BL, Leukemia, Myeloid, Acute, Mice, Tamoxifen, Proto-Oncogene Proteins c-bcl-2, Cell Line, Tumor, Tumor Cells, Cultured, Animals, Humans, Myeloid Cell Leukemia Sequence 1 Protein, Apoptosis Regulatory Proteins, Gene Deletion, Cell Proliferation
Antineoplastic Agents, Hormonal, Cell Survival, Gene Expression Regulation, Neoplastic, Mice, Inbred C57BL, Leukemia, Myeloid, Acute, Mice, Tamoxifen, Proto-Oncogene Proteins c-bcl-2, Cell Line, Tumor, Tumor Cells, Cultured, Animals, Humans, Myeloid Cell Leukemia Sequence 1 Protein, Apoptosis Regulatory Proteins, Gene Deletion, Cell Proliferation
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