--- _id: '6607' abstract: - lang: eng text: 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. article_number: '9139' article_processing_charge: No author: - first_name: Chi Huu full_name: Nguyen, Chi Huu last_name: Nguyen - first_name: Tobias full_name: Glüxam, Tobias last_name: Glüxam - first_name: Angela full_name: Schlerka, Angela last_name: Schlerka - first_name: Katharina full_name: Bauer, Katharina id: 2ED6B14C-F248-11E8-B48F-1D18A9856A87 last_name: Bauer - first_name: Alexander M. full_name: Grandits, Alexander M. last_name: Grandits - first_name: Hubert full_name: Hackl, Hubert last_name: Hackl - first_name: Oliver full_name: Dovey, Oliver last_name: Dovey - first_name: Sabine full_name: Zöchbauer-Müller, Sabine last_name: Zöchbauer-Müller - first_name: Jonathan L. full_name: Cooper, Jonathan L. last_name: Cooper - first_name: George S. full_name: Vassiliou, George S. last_name: Vassiliou - first_name: Dagmar full_name: Stoiber, Dagmar last_name: Stoiber - first_name: Rotraud full_name: Wieser, Rotraud last_name: Wieser - first_name: Gerwin full_name: Heller, Gerwin last_name: Heller citation: ama: Nguyen CH, Glüxam T, Schlerka A, et al. SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness. Scientific Reports. 2019;9(1). doi:10.1038/s41598-019-45579-0 apa: Nguyen, C. H., Glüxam, T., Schlerka, A., Bauer, K., Grandits, A. M., Hackl, H., … Heller, G. (2019). SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness. Scientific Reports. Nature Publishing Group. https://doi.org/10.1038/s41598-019-45579-0 chicago: Nguyen, Chi Huu, Tobias Glüxam, Angela Schlerka, Katharina Bauer, Alexander M. Grandits, Hubert Hackl, Oliver Dovey, et al. “SOCS2 Is Part of a Highly Prognostic 4-Gene Signature in AML and Promotes Disease Aggressiveness.” Scientific Reports. Nature Publishing Group, 2019. https://doi.org/10.1038/s41598-019-45579-0. ieee: C. H. Nguyen et al., “SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness,” Scientific Reports, vol. 9, no. 1. Nature Publishing Group, 2019. ista: Nguyen CH, Glüxam T, Schlerka A, Bauer K, Grandits AM, Hackl H, Dovey O, Zöchbauer-Müller S, Cooper JL, Vassiliou GS, Stoiber D, Wieser R, Heller G. 2019. SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness. Scientific Reports. 9(1), 9139. mla: Nguyen, Chi Huu, et al. “SOCS2 Is Part of a Highly Prognostic 4-Gene Signature in AML and Promotes Disease Aggressiveness.” Scientific Reports, vol. 9, no. 1, 9139, Nature Publishing Group, 2019, doi:10.1038/s41598-019-45579-0. short: C.H. Nguyen, T. Glüxam, A. Schlerka, K. Bauer, A.M. Grandits, H. Hackl, O. Dovey, S. Zöchbauer-Müller, J.L. Cooper, G.S. Vassiliou, D. Stoiber, R. Wieser, G. Heller, Scientific Reports 9 (2019). date_created: 2019-07-07T21:59:19Z date_published: 2019-06-24T00:00:00Z date_updated: 2023-08-28T12:26:51Z day: '24' ddc: - '576' department: - _id: PreCl doi: 10.1038/s41598-019-45579-0 external_id: isi: - '000472597400042' file: - access_level: open_access checksum: 3283522fffadf4b5fc8c7adfe3ba4564 content_type: application/pdf creator: kschuh date_created: 2019-07-08T15:15:28Z date_updated: 2020-07-14T12:47:34Z file_id: '6623' file_name: nature_2019_Nguyen.pdf file_size: 2017352 relation: main_file file_date_updated: 2020-07-14T12:47:34Z has_accepted_license: '1' intvolume: ' 9' isi: 1 issue: '1' language: - iso: eng month: '06' oa: 1 oa_version: Published Version publication: Scientific Reports publication_status: published publisher: Nature Publishing Group quality_controlled: '1' scopus_import: '1' status: public title: SOCS2 is part of a highly prognostic 4-gene signature in AML and promotes disease aggressiveness tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 9 year: '2019' ...