Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Prognostic gene signature for AML

ABSTRACT: Acute myeloid leukemia (AML) is a heterogeneous disease in respect of molecular aberrations and prognosis. We used gene expression profiling of 562 patients treated in the German AMLCG 1999 trial to develop a gene signature that predicts survival in AML. Analysis of 562 samples (140 HGU-133plus2; 422 HGU-133A; 422 HGU-133B) from adult patients with acute myeloid leukemia (AML).

ORGANISM(S): Homo sapiens

SUBMITTER: Tobias Herold

PROVIDER: E-GEOD-37642 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Identification of a 24-gene prognostic signature that improves the European LeukemiaNet risk classification of acute myeloid leukemia: an international collaborative study.

Li Zejuan Z Herold Tobias T He Chunjiang C Valk Peter J M PJ Chen Ping P Jurinovic Vindi V Mansmann Ulrich U Radmacher Michael D MD Maharry Kati S KS Sun Miao M Yang Xinan X Huang Hao H Jiang Xi X Sauerland Maria-Cristina MC Büchner Thomas T Hiddemann Wolfgang W Elkahloun Abdel A Neilly Mary Beth MB Zhang Yanming Y Larson Richard A RA Le Beau Michelle M MM Caligiuri Michael A MA Döhner Konstanze K Bullinger Lars L Liu Paul P PP Delwel Ruud R Marcucci Guido G Lowenberg Bob B Bloomfield Clara D CD Rowley Janet D JD Bohlander Stefan K SK Chen Jianjun J

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20130204 9

<h4>Purpose</h4>To identify a robust prognostic gene expression signature as an independent predictor of survival of patients with acute myeloid leukemia (AML) and use it to improve established risk classification.<h4>Patients and methods</h4>Four independent sets totaling 499 patients with AML carrying various cytogenetic and molecular abnormalities were used as training sets. Two independent patient sets composed of 825 patients were used as validation sets. Notably, patients from different se ...[more]

PMID: 23382473

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Project description:PURPOSE: Inhibitors of histone deacetylases (HDACIs) like valproic acid (VPA) display activity in murine leukemia models, and induce tumor-selective cytoxicity against blasts from patients with acute myeloid leukemia (AML). However, despite of the existing knowledge of the potential function of HDACIs, there remain many unsolved questions especially regarding the factors that determine whether a cancer cell undergoes cell cycle arrest, differentiation, or death in response to HDACIs. Furthermore, there is still limited data on HDACIs effects in vivo, as well as HDACIs function in combination with standard induction chemotherapy, as most studies evaluated HDACIs as single agent in vitro. Thus, our first goal was to determine a VPA response signature in different myeloid leukemia cell lines in vitro, followed by an in vivo analysis of VPA effects in blasts from adult de novo AML patients entered within two randomized multicenter treatment trials of the German-Austrian AML Study Group. PATIENTS AND METHODS: To define a VPA in vitro response signature we profiled gene expression in myeloid leukemia cell lines (HL60, NB4, HEL, and K-562) following 48 hours of VPA treatment by using DNA Microarray technology. Next, we evaluated the VPA effects on gene expression in AML samples collected within the AMLSG 07-04 trial for younger (age<60yrs) and within the AMLSG 06-04 trial for older adults (age>60yrs), in which patients are randomized to receive standard induction chemotherapy (idarubicine, cytarabine, and etoposide = ICE) with or without concomitant VPA. We profiled gene expression in diagnostic AML blasts and following 48 hours of treatment with ICE or ICE/VPA. cDNA microarrays from the Stanford Functional Genomics Facility were used to perform mRNA transcript profiling of 4 leukemia cell lines treated with 1mM VPA for 48 hours in comparison to untreated cell lines, and to perform mRNA transcript profiling of freshly-frozen, from matched acute myeloid leukemia peripheral blood specimens collected from 14 AML patients at diagnosis and following 48 hours of treatment with either chemotherapy +/- VPA.

Dataset Information

Prognostic gene signature for AML

Publications

Identification of a 24-gene prognostic signature that improves the European LeukemiaNet risk classification of acute myeloid leukemia: an international collaborative study.

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