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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Nguyen, Chi Huu 
Glüxam, Tobias 
Schlerka, Angela 
Bauer, Katharina 
Grandits, Alexander M 

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.

Description

Keywords

Animals, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Humans, Leukemia, Myeloid, Acute, Mice, Neoplastic Stem Cells, Prognosis, Suppressor of Cytokine Signaling Proteins

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

9

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MC_PC_12009)