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Long non-coding RNA expression profile in cytogenetically normal acute myeloid leukemia identifies a distinct signature and a new biomarker in NPM1-mutated patients
| Content Provider | Semantic Scholar |
|---|---|
| Author | Clara, Etienne De Gourvest, Morgane Ma, Hanjing Vergez, François Tosolini, Marie Déjean, Sébastien Demur, Cécile Delabesse, Eric Récher, Christian Touriol, Christian Martelli, Maria Paola Falini, Brunangelo Brousset, P. Bousquet, M. Cocaign |
| Copyright Year | 2017 |
| Abstract | Long non-coding RNAs are defined as transcripts larger than 200 nucleotides but without protein-coding potential. There is growing evidence of the important role of long non-coding RNAs in cancer initiation, development and progression. In this study, we sought to evaluate the long non-coding RNA expression profile of patients with cytogenetically normal acute myeloid leukemia (AML). RNA-sequencing of 40 cytogenetically normal AML patients allowed us to quantify 11,036 long non-coding RNAs. Among these, more than 8000 were previously undescribed long non-coding RNAs. Using unsupervised analysis, we observed a specific long non-coding RNA expression profile dependent on the mutational status of the NPM1 gene. Statistical analysis allowed us to identify a minimal set of 12 long non-coding RNAs capable of discriminating NPM1-mutated from NPM1-wild-type patients. These results were validated by qRT-PCR on an independent cohort composed of 134 cytogenetically normal AML patients. Furthermore, we have identified one putative biomarker, the long non-coding RNA XLOC_109948 whose expression pattern predicts clinical outcome. Interestingly, low XLOC_109948 expression indicates a good prognosis especially for NPM1-mutated patients. Transient transfection of GapmeR against XLOC_109948 in NPM1-mutated OCI-AML3 cell line treated with Ara-C or ATRA enhances apoptosis suggesting XLOC_109948 plays a role in drug sensitivity. This study improves our knowledge of the long non-coding RNA transcriptome in cytogenetically normal AML patients. We observed a distinct long non-coding RNA expression profile in patients with the NPM1 mutation. The newly identified XLOC_109948 long non-coding RNA emerged as a strong prognostic factor able to better stratify NPM1-mutated patients. |
| Starting Page | 1718 |
| Ending Page | 1726 |
| Page Count | 9 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/99/00/1021718.PMC5622856.pdf |
| PubMed reference number | 28679652 |
| Alternate Webpage(s) | https://doi.org/10.3324/haematol.2017.171645 |
| DOI | 10.3324/haematol.2017.171645 |
| Journal | Haematologica |
| Volume Number | 102 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Apoptosis Biological Markers Biopolymer Sequencing Fludarabine phosphate Forecast of outcome Frameshift Mutation function Large Leukemia, Myelocytic, Acute Long Intergenic Non-Protein Coding RNA Myeloid Leukemia NPM1 wt Allele Neoplasms Nucleotides Ocular Comfort Index Questionnaire Patients Prognostic Factors RNA, Long Untranslated RNA, Untranslated RUNX2 gene Transcript Transcription Initiation Transcription, Genetic non-T, non-B childhood acute lymphoblastic leukemia |
| Content Type | Text |
| Resource Type | Article |
