An mRNA expression signature for prognostication in de novo acute myeloid leukemia patients with normal karyotype
Journal
Oncotarget
Journal Volume
6
Journal Issue
36
Pages
39098-39110
Date Issued
2015
Author(s)
Chiu Y.-C.
Tseng M.-H.
Kuo Y.-Y.
Chen Y.
Chuang E.Y.
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.
SDGs
Other Subjects
messenger RNA; messenger RNA; acute myeloblastic leukemia; adolescent; adult; AIF1L gene; Article; cancer chemotherapy; cancer prognosis; cohort analysis; comparative study; CXCR7 gene; DNTT gene; female; gene; gene expression profiling; gene function; genetic association; genetic identification; GPR56 gene; H1F0 gene; human; IFITM3 gene; induction chemotherapy; karyotype; KIAA0125 gene; major clinical study; male; MX1 gene; overall survival; risk assessment; scoring system; STAB1 gene; survival rate; TM4SF1 gene; TNS3 gene; treatment response; acute myeloid leukemia; biosynthesis; genetics; karyotyping; metabolism; middle aged; prognosis; survival analysis; Female; Humans; Karyotyping; Leukemia, Myeloid, Acute; Male; Middle Aged; Prognosis; RNA, Messenger; Survival Analysis
Type
journal article