Overexpression of the ETS-related gene, ERG, predicts a worse outcome in acute myeloid leukemia with normal karyotype: a Cancer and Leukemia Group B study.
OBJECTIVE
To test the prognostic significance of ETS-related gene (ERG) expression in cytogenetically normal primary acute myeloid leukemia (AML).


METHODS
Pretreatment blood samples from 84 cytogenetically normal AML patients aged less than 60 years, who were characterized for BAALC expression, FLT3 internal tandem duplication (ITD), and MLL partial tandem duplication (PTD) and uniformly treated on Cancer and Leukemia Group B 9621 protocol, were analyzed for ERG expression by real-time reverse transcriptase polymerase chain reaction. Patients were divided into quartiles according to ERG levels and were compared for clinical outcome. High-density oligonucleotide arrays were used to identify genes differentially expressed between high and low ERG expressers.


RESULTS
With a median follow-up of 5.7 years, patients with the upper 25% of ERG expression values had a worse cumulative incidence of relapse (CIR; P < .001) and overall survival (OS; P = .011) than the remaining patients. In a multivariable analysis, high ERG expression (P < .001) and the presence of MLL PTD (P = .027) predicted worse CIR. With regard to OS, an interaction was observed between expression of ERG and BAALC (P = .013), with ERG overexpression predicting shorter survival only in low BAALC expressers (P = .002). ERG overexpression was an independent prognostic factor even when the unfavorable group of FLT3 ITD patients lacking an FLT3 wild-type allele was included. High ERG expression was associated with upregulation of 112 expressed-sequenced tags and named genes, many of which are involved in cell proliferation, differentiation, and apoptosis.


CONCLUSIONS
ERG overexpression in AML patients with normal cytogenetics predicts an adverse clinical outcome and seems to be associated with a specific molecular signature.
Marcucci
Guido
G
Division of Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus OH 43210, USA. marcucci-1@medctr.osu.edu
Baldus
Claudia D
CD
Ruppert
Amy S
AS
Radmacher
Michael D
MD
Mrózek
Krzysztof
K
Whitman
Susan P
SP
Kolitz
Jonathan E
JE
Edwards
Colin G
CG
Vardiman
James W
JW
Powell
Bayard L
BL
Baer
Maria R
MR
Moore
Joseph O
JO
Perrotti
Danilo
D
Caligiuri
Michael A
MA
Carroll
Andrew J
AJ
Larson
Richard A
RA
de la Chapelle
Albert
A
Bloomfield
Clara D
CD
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D020224:Expressed Sequence Tags; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D000071230:Transcriptional Regulator ERG; D015854:Up-Regulation
D004268:DNA-Binding Proteins; C072312:ERG protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG