An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia
Open Access
- 15 November 2008
- journal article
- clinical trial
- Published by American Society of Hematology in Blood
- Vol. 112 (10), 4193-4201
- https://doi.org/10.1182/blood-2008-02-134411
Abstract
Patients with cytogenetically normal acute myeloid leukemia (CN-AML) show heterogeneous treatment outcomes. We used gene-expression profiling to develop a gene signature that predicts overall survival (OS) in CN-AML. Based on data from 163 patients treated in the German AMLCG 1999 trial and analyzed on oligonucleotide microarrays, we used supervised principal component analysis to identify 86 probe sets (representing 66 different genes), which correlated with OS, and defined a prognostic score based on this signature. When applied to an independent cohort of 79 CN-AML patients, this continuous score remained a significant predictor for OS (hazard ratio [HR], 1.85; P = .002), event-free survival (HR = 1.73; P = .001), and relapse-free survival (HR = 1.76; P = .025). It kept its prognostic value in multivariate analyses adjusting for age, FLT3 ITD, and NPM1 status. In a validation cohort of 64 CN-AML patients treated on CALGB study 9621, the score also predicted OS (HR = 4.11; P < .001), event-free survival (HR = 2.90; P < .001), and relapse-free survival (HR = 3.14, P < .001) and retained its significance in a multivariate model for OS. In summary, we present a novel gene-expression signature that offers additional prognostic information for patients with CN-AML.Keywords
This publication has 34 references indexed in Scilit:
- An FLT3 gene-expression signature predicts clinical outcome in normal karyotype AMLBlood, 2008
- A microarray study of altered gene expression after cytarabine resistance in acute myeloid leukemiaLeukemia, 2007
- Comparison of gene-expression profiles in parallel bone marrow and peripheral blood samples in acute myeloid leukaemia by real-time polymerase chain reactionJournal of Clinical Pathology, 2006
- Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification?Blood, 2006
- Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome predictionBlood, 2006
- Double Induction Containing Either Two Courses or One Course of High-Dose Cytarabine Plus Mitoxantrone and Postremission Therapy by Either Autologous Stem-Cell Transplantation or by Prolonged Maintenance for Acute Myeloid LeukemiaJournal of Clinical Oncology, 2006
- Independent confirmation of a prognostic gene-expression signature in adult acute myeloid leukemia with a normal karyotype: a Cancer and Leukemia Group B studyBlood, 2006
- Distinct gene expression patterns associated with FLT3- and NRAS-activating mutations in acute myeloid leukemia with normal karyotypeOncogene, 2005
- Dose Escalation Studies of Cytarabine, Daunorubicin, and Etoposide With and Without Multidrug Resistance Modulation With PSC-833 in Untreated Adults With Acute Myeloid Leukemia Younger Than 60 Years: Final Induction Results of Cancer and Leukemia Group B Study 9621Journal of Clinical Oncology, 2004
- Semi-Supervised Methods to Predict Patient Survival from Gene Expression DataPLoS Biology, 2004