دورية أكاديمية
Prognostic and biologic significance of DNMT3B expression in older patients with cytogenetically normal primary acute myeloid leukemia
| العنوان: | Prognostic and biologic significance of DNMT3B expression in older patients with cytogenetically normal primary acute myeloid leukemia |
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| المؤلفون: | Niederwieser, C, Kohlschmidt, J., VOLINIA, Stefano, Whitman, S. P., Metzeler, K. H., Eisfeld, A. K., Maharry, K., Yan, P., Frankhouser, D., Becker, H., Schwind, S., Carroll, A. J., Nicolet, D., Mendler, J. H., Curfman, J. P., Wu, Y. Z., Baer, M. R., Powell, B. L., Kolitz, J. E., Moore, J. O., Carter, T. H., Bundschuh, R., Larson, R. A., Stone, R. M., Mrózek, K., Marcucci, G., Bloomfield, C. D. |
| المساهمون: | Niederwieser, C, Kohlschmidt, J., Volinia, Stefano, Whitman, S. P., Metzeler, K. H., Eisfeld, A. K., Maharry, K., Yan, P., Frankhouser, D., Becker, H., Schwind, S., Carroll, A. J., Nicolet, D., Mendler, J. H., Curfman, J. P., Wu, Y. Z., Baer, M. R., Powell, B. L., Kolitz, J. E., Moore, J. O., Carter, T. H., Bundschuh, R., Larson, R. A., Stone, R. M., Mrózek, K., Marcucci, G., Bloomfield, C. D. |
| سنة النشر: | 2015 |
| المجموعة: | Università degli Studi di Ferrara: CINECA IRIS |
| مصطلحات موضوعية: | noAge Factor, Aged, 80 and over, Cytarabine, DNA (Cytosine-5-)-Methyltransferase, DNA Methylation, Daunorubicin, Female, Gene Expression Profiling, Human, Induction Chemotherapy, Karyotyping, Leukemia, Myeloid, Acute, Male, MicroRNA, Microarray Analysi, Middle Aged, Prognosi, Survival Analysi, Gene Expression Regulation, Leukemic |
| الوصف: | DNMT3B encodes a DNA methyltransferase implicated in aberrant epigenetic changes contributing to leukemogenesis. We tested whether DNMT3B expression, measured by NanoString nCounter assay, associates with outcome, gene and microRNA expression and DNA methylation profiles in 210 older (≥60 years) adults with primary, cytogenetically normal acute myeloid leukemia (CN-AML). Patients were dichotomized into high versus low expressers using median cut. Outcomes were assessed in the context of known CN-AML prognosticators. Gene and microRNA expression, and DNA methylation profiles were analyzed using microarrays and MethylCap-sequencing, respectively. High DNMT3B expressers had fewer complete remissions (CR; P=0.002) and shorter disease-free (DFS; P=0.02) and overall (OS; P<0.001) survival. In multivariable analyses, high DNMT3B expression remained an independent predictor of lower CR rates (P=0.04) and shorter DFS (P=0.04) and OS (P=0.001). High DNMT3B expression associated with a gene expression profile comprising 363 genes involved in differentiation, proliferation and survival pathways, but with only four differentially expressed microRNAs (miR-133b, miR-148a, miR-122, miR-409-3p) and no differential DNA methylation regions. We conclude that high DNMT3B expression independently associates with adverse outcome in older CN-AML patients. Gene expression analyses suggest that DNMT3B is involved in the modulation of several genes, although the regulatory mechanisms remain to be investigated to devise therapeutic approaches specific for these patients. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | STAMPA |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/25204569; info:eu-repo/semantics/altIdentifier/wos/WOS:000350734300006; volume:29; issue:3; firstpage:567; lastpage:575; numberofpages:9; journal:LEUKEMIA; http://hdl.handle.net/11392/2356328Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84924599811; https://www.nature.com/articles/leu2014267Test |
| DOI: | 10.1038/leu.2014.267 |
| الإتاحة: | https://doi.org/10.1038/leu.2014.267Test http://hdl.handle.net/11392/2356328Test https://www.nature.com/articles/leu2014267Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.E8B9E3C4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/leu.2014.267 |
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