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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.

Publication ,  Journal Article
Marcucci, G; Baldus, CD; Ruppert, AS; Radmacher, MD; Mrózek, K; Whitman, SP; Kolitz, JE; Edwards, CG; Vardiman, JW; Powell, BL; Baer, MR ...
Published in: J Clin Oncol
December 20, 2005

PURPOSE: To test the prognostic significance of ETS-related gene (ERG) expression in cytogenetically normal primary acute myeloid leukemia (AML). PATIENTS AND 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. CONCLUSION: ERG overexpression in AML patients with normal cytogenetics predicts an adverse clinical outcome and seems to be associated with a specific molecular signature.

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Published In

J Clin Oncol

DOI

ISSN

0732-183X

Publication Date

December 20, 2005

Volume

23

Issue

36

Start / End Page

9234 / 9242

Location

United States

Related Subject Headings

  • Up-Regulation
  • Transcriptional Regulator ERG
  • Trans-Activators
  • Survival Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Prognosis
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Leukemia, Myeloid
 

Citation

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MLA
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Marcucci, G., Baldus, C. D., Ruppert, A. S., Radmacher, M. D., Mrózek, K., Whitman, S. P., … Bloomfield, C. D. (2005). 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. J Clin Oncol, 23(36), 9234–9242. https://doi.org/10.1200/JCO.2005.03.6137
Marcucci, Guido, Claudia D. Baldus, Amy S. Ruppert, Michael D. Radmacher, Krzysztof Mrózek, Susan P. Whitman, Jonathan E. Kolitz, et al. “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.J Clin Oncol 23, no. 36 (December 20, 2005): 9234–42. https://doi.org/10.1200/JCO.2005.03.6137.
Marcucci G, Baldus CD, Ruppert AS, Radmacher MD, Mrózek K, Whitman SP, et al. 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. J Clin Oncol. 2005 Dec 20;23(36):9234–42.
Marcucci, Guido, et al. “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.J Clin Oncol, vol. 23, no. 36, Dec. 2005, pp. 9234–42. Pubmed, doi:10.1200/JCO.2005.03.6137.
Marcucci G, Baldus CD, Ruppert AS, Radmacher MD, Mrózek K, Whitman SP, Kolitz JE, Edwards CG, Vardiman JW, Powell BL, Baer MR, Moore JO, Perrotti D, Caligiuri MA, Carroll AJ, Larson RA, de la Chapelle A, Bloomfield CD. 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. J Clin Oncol. 2005 Dec 20;23(36):9234–9242.

Published In

J Clin Oncol

DOI

ISSN

0732-183X

Publication Date

December 20, 2005

Volume

23

Issue

36

Start / End Page

9234 / 9242

Location

United States

Related Subject Headings

  • Up-Regulation
  • Transcriptional Regulator ERG
  • Trans-Activators
  • Survival Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Prognosis
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Leukemia, Myeloid