An mRNA expression signature for prognostication in de novo acute myeloid leukemia patients with normal karyotype

Ming Kai Chuang, Yu Chiao Chiu, Wen Chien Chou, Hsin An Hou, Mei Hsuan Tseng, Yi Yi Kuo, Yidong Chen, Eric Y. Chuang, Hwei Fang Tien

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Although clinical features, cytogenetics, and mutations are widely used to predict prognosis in patients with acute myeloid leukemia (AML), further refinement of risk stratification is necessary for optimal treatment, especially in cytogenetically normal (CN) patients. We sought to generate a simple gene expression signature as a predictor of clinical outcome through analyzing the mRNA arrays of 158 de novo CN AML patients. We compared the gene expression profiles of patients with poor response to induction chemotherapy with those who responded well. Forty-six genes expressed differentially between the two groups. Among them, expression of 11 genes was significantly associated with overall survival (OS) in univariate Cox regression analysis in 104 patients who received standard intensive chemotherapy. We integrated the z-transformed expression levels of these 11 genes to generate a risk scoring system. Higher risk scores were significantly associated with shorter OS (median 17.0 months vs. not reached, P < 0.001) in ours and another 3 validation cohorts. In addition, it was an independent unfavorable prognostic factor by multivariate analysis (HR 1.116, 95% CI 1.035~1.204, P = 0.004). In conclusion, we developed a simple mRNA expression signature for prognostication in CN-AML patients. This prognostic biomarker will help refine the treatment strategies for this group of patients.

Original languageEnglish (US)
Pages (from-to)39098-39110
Number of pages13
JournalOncotarget
Volume6
Issue number36
DOIs
StatePublished - 2015

Keywords

  • Acute myeloid leukemia
  • Normal cytogenetics
  • Prognosis
  • mRNA signature

ASJC Scopus subject areas

  • Oncology

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    Chuang, M. K., Chiu, Y. C., Chou, W. C., Hou, H. A., Tseng, M. H., Kuo, Y. Y., Chen, Y., Chuang, E. Y., & Tien, H. F. (2015). An mRNA expression signature for prognostication in de novo acute myeloid leukemia patients with normal karyotype. Oncotarget, 6(36), 39098-39110. https://doi.org/10.18632/oncotarget.5390