Development of gene expression-based risk score in cytogenetically normal acute myeloid leukemia patients.
Patients with normal karyotype represent the single largest cytogenetic group of acute myeloid leukemia (AML), with highly heterogeneous clinical and molecular characteristics. In this study, we sought to determine new prognostic biomarkers in cytogenetically normal (CN)-AML patients. A gene expression (GE)-based risk score was built, summing up the prognostic value of 22 genes whose expression is associated with a bad prognosis in a training cohort of 163 patients. GE-based risk score allowed identifying a high-risk group of patients (53.4%) in two independent cohorts of CN-AML patients. GE-based risk score and EVI1 gene expression remained independent prognostic factors using multivariate Cox analyses. Combining GE-based risk score with EVI1 gene expression allowed the identification of three clinically different groups of patients in two independent cohorts of CN-AML patients. Thus, GE-based risk score is powerful to predict clinical outcome for CN-AML patients and may provide potential therapeutic advances.
Groupe d'études des transcriptomes, Université MONTPELLIER 2, Montpellier, F-34197 France .
Elias
E
Bou Samra
Bernard
B
Klein
Thérèse
T
Commes
Jérôme
J
Moreaux
D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D018572:Disease-Free Survival; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics*; D000074008:MDS1 and EVI1 Complex Locus Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011379:Prognosis; D011519:Proto-Oncogenes / Q000235:genetics*; D012306:Risk; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D000071230:Transcriptional Regulator ERG; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics
C442828:BAALC protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; C506524:MN1 protein, human; D009363:Neoplasm Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG; D025521:Tumor Suppressor Proteins