Prognostic importance of MN1 transcript levels, and biologic insights from MN1-associated gene and microRNA expression signatures in cytogenetically normal acute myeloid leukemia: a cancer and leukemia group B study.
PURPOSE To determine the prognostic importance of the meningioma 1 (MN1) gene expression levels in the context of other predictive molecular markers, and to derive MN1 associated gene- and microRNA-expression profiles in cytogenetically normal acute myeloid leukemia (CN-AML). PATIENTS AND METHODS MN...
| Publicado en: | Journal of Clinical Oncology Vol. 27; no. 19; pp. 3198 - 3205 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
American Society of Clinical Oncology
7/1/2009
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105374915&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105374915 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 0732183X 20D jtl: Journal of Clinical Oncology issn: 0732183X maglogo: N pubinfo: dt: 7/1/2009 vid: 27 iid: 19 pid: 26892 pub: American Society of Clinical Oncology place: Alexandria, Virginia artinfo: ui: 105374915 105374915 NLM19451432 2010334167 10.1200/JCO.2008.20.6110 NLM19451432 PMC2716941 105374915 ppf: 3198 ppct: 7 formats: tig: atl: Prognostic importance of MN1 transcript levels, and biologic insights from MN1-associated gene and microRNA expression signatures in cytogenetically normal acute myeloid leukemia: a cancer and leukemia group B study. aug: au: Langer C Marcucci G Holland KB Radmacher MD Maharry K Paschka P Whitman SP Mrózek K Baldus CD Vij R Powell BL Carroll AJ Kolitz JE Caligiuri MA Larson RA Bloomfield CD Langer, Christian Marcucci, Guido Holland, Kelsi B Radmacher, Michael D affil: Division of Hematology and Oncology, Comprehensive Cancer Center, The Ohio State University, Suite A434 Starling-Loving Hall, 320 W 10th Avenue, Columbus, OH 43210, USA sug: subj: Genetic Techniques Leukemia, Myeloid, Acute Proteins RNA Adolescence Adult Biochips Female Kaplan-Meier Estimator Leukemia, Myeloid, Acute Mortality Male Middle Age Oncogenes Prognosis Reverse Transcriptase Polymerase Chain Reaction Transferases Human Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Female Male ab: PURPOSE To determine the prognostic importance of the meningioma 1 (MN1) gene expression levels in the context of other predictive molecular markers, and to derive MN1 associated gene- and microRNA-expression profiles in cytogenetically normal acute myeloid leukemia (CN-AML). PATIENTS AND METHODS MN1 expression was measured in 119 untreated primary CN-AML adults younger than 60 years by real-time reverse-transcriptase polymerase chain reaction. Patients were also tested for FLT3, NPM1, CEBPA, and WT1 mutations, MLL partial tandem duplications, and BAALC and ERG expression. Gene- and microRNA-expression profiles were attained by performing genome-wide microarray assays. Patients were intensively treated on two first-line Cancer and Leukemia Group B clinical trials. Results Higher MN1 expression associated with NPM1 wild-type (P < .001), increased BAALC expression (P = .004), and less extramedullary involvement (P = .01). In multivariable analyses, higher MN1 expression associated with a lower complete remission rate (P = .005) after adjustment for WBC; shorter disease-free survival (P = .01) after adjustment for WT1 mutations, FLT3 internal tandem duplications (FLT3-ITD), and high ERG expression; and shorter survival (P = .04) after adjustment for WT1 and NPM1 mutations, FLT3-ITD, and WBC. Gene- and microRNA-expression profiles suggested that high MN1 expressers share features with high BAALC expressers and patients with wild-type NPM1. Higher MN1 expression also appears to be associated with genes and microRNAs that are active in aberrant macrophage/monocytoid function and differentiation. CONCLUSION MN1 expression independently predicts outcome in CN-AML patients. The MN1 gene- and microRNA-expression signatures suggest biologic features that could be exploited as therapeutic targets. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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