| 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. © 2012 by Cold Spring Harbor Laboratory Press. |
| Keywords: |
controlled study; protein expression; acute granulocytic leukemia; gene deletion; leukemia, myeloid, acute; nonhuman; cell proliferation; mouse; animals; mice; cell survival; mus; protein bcl 2; apoptosis; animal experiment; animal model; apoptosis regulatory proteins; tumor cells, cultured; cell line, tumor; mice, inbred c57bl; gene expression regulation, neoplastic; protein bcl w; protein mcl 1; leukemia cell; tamoxifen; antineoplastic agents, hormonal; proto-oncogene proteins c-bcl-2; pharmacological blocking; acute myeloid leukemia; bcl-xl; protein bcl x; mcl-1
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