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Sci Rep. 2019 Jun 24;9(1):9139. doi: 10.1038/s41598-019-45579-0.

SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness.

Author information

1
Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.
2
Comprehensive Cancer Center, Vienna, Austria.
3
Institute of Science and Technology Austria, Vienna, Austria.
4
Division of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
5
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
6
Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria.
7
Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
8
Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria. rotraud.wieser@meduniwien.ac.at.
9
Comprehensive Cancer Center, Vienna, Austria. rotraud.wieser@meduniwien.ac.at.
10
Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria. gerwin.heller@meduniwien.ac.at.
11
Comprehensive Cancer Center, Vienna, Austria. gerwin.heller@meduniwien.ac.at.
12
Institute of Pharmacology and Toxicology, Department for Biomedical Sciences, University of Veterinary Medicine Vienna, Vienna, Austria. gerwin.heller@meduniwien.ac.at.

Abstract

Acute myeloid leukemia (AML) is a heterogeneous disease with respect to its genetic and molecular basis and to patients´ outcome. Clinical, cytogenetic, and mutational data are used to classify patients into risk groups with different survival, however, within-group heterogeneity is still an issue. Here, we used a robust likelihood-based survival modeling approach and publicly available gene expression data to identify a minimal number of genes whose combined expression values were prognostic of overall survival. The resulting gene expression signature (4-GES) consisted of 4 genes (SOCS2, IL2RA, NPDC1, PHGDH), predicted patient survival as an independent prognostic parameter in several cohorts of AML patients (total, 1272 patients), and further refined prognostication based on the European Leukemia Net classification. An oncogenic role of the top scoring gene in this signature, SOCS2, was investigated using MLL-AF9 and Flt3-ITD/NPM1c driven mouse models of AML. SOCS2 promoted leukemogenesis as well as the abundance, quiescence, and activity of AML stem cells. Overall, the 4-GES represents a highly discriminating prognostic parameter in AML, whose clinical applicability is greatly enhanced by its small number of genes. The newly established role of SOCS2 in leukemia aggressiveness and stemness raises the possibility that the signature might even be exploitable therapeutically.

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