Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome prediction

Carla S. Wilson, George S. Davidson, Shawn B. Martin, Erik Andries, Jeffrey Potter, Richard Harvey, Kerem Ar, Yuexian Xu, Kenneth J. Kopecky, Donna P. Ankerst, Holly Gundacker, Marilyn L. Slovak, Monica Mosquera-Caro, I. Ming Chen, Derek L. Stirewalt, Maurice Murphy, Frederick A. Schultz, Huining Kang, Xuefei Wang, Jerald P. RadichFrederick R. Appelbaum, Susan R. Atlas, John Godwin, Cheryl L. Willman

Research output: Contribution to journalArticlepeer-review

140 Scopus citations

Abstract

To determine whether gene expression profiling could improve risk classification and outcome prediction in older acute myeloid leukemia (AML) patients, expression profiles were obtained in pretreatment leukemic samples from 170 patients whose median age was 65 years. Unsupervised clustering methods were used to classify patients into 6 cluster groups (designated A to F) that varied significantly in rates of resistant disease (RD; P < .001), complete response (CR; P = .023), and disease-free survival (DFS; P = .023). Cluster A (n = 24), dominated by NPM1 mutations (78%), normal karyotypes (75%), and genes associated with signaling and apoptosis, had the best DFS (27%) and overall survival (OS; 25% at 5 years). Patients in clusters B (n = 22) and C (n = 31) had the worst OS (5% and 6%, respectively); cluster B was distinguished by the highest rate of RD (77%) and multidrug resistant gene expression (ABCG2, MDR1). Cluster D was characterized by a "proliferative" gene signature with the highest proportion of detectable cytogenetic abnormalities (76%; including 83% of all favorable and 34% of unfavorable karyotypes). Cluster F (n = 33) was dominated by monocytic leukemias (97% of cases), also showing increased NPM1 mutations (61%). These gene expression signatures provide insights into novel groups of AML not predicted by traditional studies that impact prognosis and potential therapy.

Original languageEnglish (US)
Pages (from-to)685-696
Number of pages12
JournalBlood
Volume108
Issue number2
DOIs
StatePublished - Jul 15 2006

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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