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| Item Type: | Article |
|---|---|
| Title: | Analysis of NPM1 splice variants reveals differential expression patterns of prognostic value in acute myeloid leukemia |
| Creators Name: | Zajac, M. and Dolnik, A. and Stasiak, G. and Zaleska, J. and Kielbus, M. and Czapinski, J. and Schunn, M. and Correa, S.C. and Glodkowska-Mrowka, E. and Sundaram, R.C. and Jankowska-Lecka, O. and Schlenk, R.F. and Döhner, H. and Döhner, K. and Stepulak, A. and Bullinger, L. and Giannopoulos, K. |
| Abstract: | Mutations of the nucleophosmin-1 (NPM1) gene in cytogenetically normal (CN) acute myeloid leukemia (AML) identify a group of patients with more favorable prognosis. NPM1 encodes three main alternatively spliced isoforms R1(B23.1), R2(B23.2), and R3(B23.3). The expression of splice variants R1, R2 and R3 were higher in AML patients compared to normal cells of healthy volunteers (HVs), although RNA-seq analysis revealed enhanced R2 expression also in less differentiated cells of HVs as well as in AML cells. The variant R2, which lacks exons 11 and 12 coding for the nucleolar localization domain, might behave similar to the mutant form of NPM1 (NPM1mut). In accordance, in CN-AML high R2 expression was associated with favorable impact on outcome. Moreover, functional studies showed nucleolar localization of the eGFP-NPM1 wildtype and cytoplasmic localization of the eGFP-NPM1 mut protein. While the eGFP-NPM1 R2 splice variant localized predominantly in the nucleoplasm, we also could detect cytoplasmic expression for the R2 variant. These results support a unique biological consequence of R2 overexpression and in part explain our clinical observation, where that high R2 variant expression was associated with a better prognosis in CN-AML patients. |
| Keywords: | AML, Splicing Variants, NPM1 |
| Source: | Oncotarget |
| ISSN: | 1949-2553 |
| Publisher: | Impact Journals |
| Volume: | 8 |
| Number: | 56 |
| Page Range: | 95163-95175 |
| Date: | 10 November 2017 |
| Official Publication: | https://doi.org/10.18632/oncotarget.19871 |
| PubMed: | View item in PubMed |
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