Altered miRNA and gene expression in acute myeloid leukemia with complex karyotype identify networks of prognostic relevance
Recently, the p53-miR-34a network has been identified to have an important role in tumorigenesis. As in acute myeloid leukemia with complex karyotype (CK-AML) TP53 alterations are the most common known molecular lesion, we further analyzed the p53-miR-34a axis in a large cohort of CK-AML with known...
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| Hauptverfasser: | , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2013
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| In: |
Leukemia
Year: 2013, Jahrgang: 27, Heft: 2, Pages: 353-361 |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/leu.2012.208 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/leu.2012.208 Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/leu2012208 
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| Verfasserangaben: | F.G. Rücker, A.C. Russ, S. Cocciardi, H. Kett, R.F. Schlenk, U. Botzenhardt, C. Langer, J. Krauter, S. Fröhling, B. Schlegelberger, A. Ganser, P. Lichter, T. Zenz, H. Döhner, K. Döhner and L. Bullinger |
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| 245 | 1 | 0 | |a Altered miRNA and gene expression in acute myeloid leukemia with complex karyotype identify networks of prognostic relevance |c F.G. Rücker, A.C. Russ, S. Cocciardi, H. Kett, R.F. Schlenk, U. Botzenhardt, C. Langer, J. Krauter, S. Fröhling, B. Schlegelberger, A. Ganser, P. Lichter, T. Zenz, H. Döhner, K. Döhner and L. Bullinger |
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| 520 | |a Recently, the p53-miR-34a network has been identified to have an important role in tumorigenesis. As in acute myeloid leukemia with complex karyotype (CK-AML) TP53 alterations are the most common known molecular lesion, we further analyzed the p53-miR-34a axis in a large cohort of CK-AML with known TP53 status (TP53altered, n=57; TP53unaltered, n=31; altered indicates loss and/or mutation of TP53). Profiling microRNA (miRNA) expression delineated TP53 alteration-associated miRNA profiles, and identified miR-34a and miR-100 as the most significantly down- and upregulated miRNA, respectively. Moreover, we found a distinct miR-34a expression-linked gene expression profile enriched for genes belonging to p53-associated pathways, and implicated in cell cycle progression or apoptosis. Clinically, low miR-34a expression and TP53 alterations predicted for chemotherapy resistance and inferior outcome. Notably, in TP53unaltered CK-AML, high miR-34a expression predicted for inferior overall survival (OS), whereas in TP53biallelic altered CK-AML, high miR-34a expression pointed to better OS. Thus, detailed molecular profiling links impaired p53 to decreased miR-34a expression, but also identifies p53-independent miR-34a induction mechanisms as shown in TP53biallelic altered cell lines treated with 15-deoxy-Δ12,14-prostaglandin. An improved understanding of this mechanism might provide novel therapeutic options to restore miR-34a function and thereby induce cell cycle arrest and apoptosis in TP53altered CK-AML. | ||
| 650 | 4 | |a Acute myeloid leukaemia | |
| 650 | 4 | |a Cancer genomics | |
| 650 | 4 | |a Chemotherapy | |
| 650 | 4 | |a miRNAs | |
| 700 | 1 | |a Russ, A. C. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Cocciardi, S. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kett, H. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schlenk, R. F. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Botzenhardt, U. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Langer, C. |e VerfasserIn |4 aut | |
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