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MDM 2 antagonist clinical response association with a gene expression signature in acute myeloid leukaemia
Author(s) -
Zhong Hua,
Chen Gong,
Jukofsky Lori,
Geho David,
Han Sung Won,
Birzele Fabian,
Bader Sabine,
Himmelein Lucia,
Cai James,
Albertyn Zayed,
Rothe Mark,
Essioux Laurent,
Burtscher Helmut,
Middleton Steven A.,
Rueger Ruediger,
Chen LinChi,
Dangl Markus,
Nichols Gwen,
Pierceall William E.
Publication year - 2015
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13411
Subject(s) - myeloid leukaemia , antagonist , myeloid , gene signature , gene expression , signature (topology) , gene , immunology , medicine , cancer research , biology , genetics , receptor , geometry , mathematics
Acute myeloid leukaemia (AML) is uniquely sensitive to p53 activation 1, 2 as ≈90% of patients carry wild-type TP53 and frequent MDM2 overexpression.3 MDM2 blocks p53 transactivation and targets p53 for ubiquitin-dependent degradation.4, 5 Nutlins have been characterized as potent and selective small-molecule MDM2 antagonists.1, 6–8 RG7112 was the first such MDM2 antagonist to undergo clinical assessment in solid tumors and leukaemia trials.1, 2, 9 As not all patients with functional p53 will respond to MDM2 antagonists, diagnostic tools may identify patients likely to respond.