High BRE expression predicts favorable outcome in adult acute myeloid leukemia, in particular among MLL-AF9-positive patients

被引：24

作者：

Noordermeer, Sylvie M. ^{[1
]}

Sanders, Mathijs A. ^{[2
]}

Gilissen, Christian ^{[3
]}

Tonnissen, Evelyn ^{[1
]}

van der Heijden, Adrian ^{[1
]}

Doehner, Konstanze ^{[4
]}

Bullinger, Lars ^{[4
]}

Jansen, Joop H. ^{[1
]}

Valk, Peter J. M. ^{[2
]}

van der Reijden, Bert A. ^{[1
]}

机构：

[1] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, Dept Lab Med,Lab Hematol, NL-6525 ED Nijmegen, Netherlands

[2] Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands

[3] Radboud Univ Nijmegen, Med Ctr, Inst Genet & Metab Disorders, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands

[4] Univ Ulm, Dept Internal Med 3, D-7900 Ulm, Germany

来源：

BLOOD | 2011年 / 118卷 / 20期

关键词：

ACUTE MYELOGENOUS LEUKEMIA; E3 UBIQUITIN LIGASES; MULTIPLE-MYELOMA; MUTATIONS; PROTEIN; AML; TRANSFORMATION; COMPLEX; FAMILY; BOX;

D O I：

10.1182/blood-2011-06-359182

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Aberrations in protein ubiquitination have recently been identified in the pathogenesis of acute myeloid leukemia (AML). We studied whether expression changes of more than 1600 ubiquitination related genes correlated with clinical outcome in 525 adult AML patients. High expression of one of these genes, BRE, was observed in 3% of the cases and predicted favorable prognosis independently of known prognostic factors (5-year overall survival: 57%). Remarkably, unsupervised expression profiling showed that 86% of high BRE-expressing patients were confined to a previously unrecognized cluster. High BRE expression was mutually exclusive with FLT3 ITD, CEBPA, IDH1, and IDH2 mutations, EVI1 overexpression, and favorable karyotypes. In contrast, high BRE expression co-occurred strongly with FAB M5 morphology and MLL-AF9 fusions. Within the group of MLL-AF9-positive patients, high BRE expression predicted superior survival, while normal BRE expression predicted extremely poor survival (5-year overall survival of 80% vs 0%, respectively, P = .0002). Both the co-occurrence of high BRE expression with MLL-AF9 and its prognostic impact were confirmed in an independent cohort of 436 AML patients. Thus, high BRE expression defines a novel subtype of adult AML characterized by a favorable prognosis. This work contributes to improved risk stratification in AML, especially among MLL-AF9-positive patients. (Blood. 2011;118(20):5613-5621)

引用

页码：5613 / 5621

页数：9

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