An mRNA expression signature for prognostication inde novoacute myeloid leukemia patients with normal karyotype

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.

High expression of dedicator of cytokinesis 1 (DOCK1) confers poor prognosis in acute myeloid leukemia

“…To further evaluate the potential of DOCK1 expression as a prognostic marker for AML, we compared the survival impact of DOCK1 expression with other published gene expression-based prognostic signatures. We performed pairwise multivariate Cox analysis of DOCK1 expression with each of the published 3-gene, [ 12 ] 7-gene, [ 13 ] 11-gene, [ 14 ] and 24-gene predictors [ 15 ]. Notably, DOCK1 expression remained a prognostic factor independent to all these composite signatures (with multivariate Cox p<0.05) and achieved even higher significance in most of the comparison settings (10 out of 12; Table 3 ).…”

CDH1 (E-cadherin) expression independently affects clinical outcome in acute myeloid leukemia with normal cytogenetics

“…The presence of specific cytogenetic abnormalities, such as t(15;17), t (8;21) or inv(16)/t (16;16), predicts a favorable prognosis, whereas t(9;22), 11q23 abnormalities, -5/5q-, -7/7q-, or complex karyotypes have adverse impact on clinical outcome in de novo AML patients [4]. Unfortunately, although several cytogenetic factors have been widely incorporated into clinical consideration for choosing treatment regimens, approximately one-half of the patients are cytogenetically normal patients which are usually assigned to intermediate prognostic group [5,6]. Besides gene mutations (CEBPA, NPM1, C-KIT, FLT3, etc.…”

High expression of CD52 predicts poor prognosis of cytogenetic normal acute myeloid leukemia

“…There were no significant differences between the two groups in sex, race, FAB classification, chemotherapy, transplant, genetic mutations (NPM1, FLT3, IDH1, IDH2, RUNX1) (all P value > 0.05). The baseline characteristics patients in GSE12417 and GSE71014 had already described in previous studies (18,19). Kaplan-Meier survival curves suggested that CD52 high was an adverse factor for chemotherapy group (EFS, p = 0.041; OS, p = 0.013; Fig.…”