title: Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia.
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.affiliation: The Walter and Eliza Hall Institute, Parkville, Melbourne, Victoria 3052, Australia.
authors.forename: Stefan P
authors.initials: SP
authors.lastname: Glaser
authors.forename: Erinna F
authors.initials: EF
authors.lastname: Lee
authors.forename: Evelyn
authors.initials: E
authors.lastname: Trounson
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouillet
authors.forename: Andrew
authors.initials: A
authors.lastname: Wei
authors.forename: W Douglas
authors.initials: WD
authors.lastname: Fairlie
authors.forename: David J
authors.initials: DJ
authors.lastname: Izon
authors.forename: Johannes
authors.initials: J
authors.lastname: Zuber
authors.forename: Amy R
authors.initials: AR
authors.lastname: Rappaport
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Herold
authors.forename: Warren S
authors.initials: WS
authors.lastname: Alexander
authors.forename: Scott W
authors.initials: SW
authors.lastname: Lowe
authors.forename: Lorraine
authors.initials: L
authors.lastname: Robb
authors.forename: Andreas
authors.initials: A
authors.lastname: Strasser
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D018931:Antineoplastic Agents, Hormonal; D051017:Apoptosis Regulatory Proteins; C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D013629:Tamoxifen