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Haematologica. 2017 Oct;102(10):1718-1726. doi: 10.3324/haematol.2017.171645. Epub 2017 Jul 4.

Long non-coding RNA expression profile in cytogenetically normal acute myeloid leukemia identifies a distinct signature and a new biomarker in NPM1-mutated patients.

Author information

1
Cancer Research Center of Toulouse (CRCT), UMR1037 Inserm/Université Toulouse III Paul Sabatier, ERL5294 CNRS, Laboratoire d'Excellence Toulouse Cancer (TOUCAN), France.
2
BGI, Shenzhen, China.
3
Laboratoire et Service d'Hématologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer, France.
4
Institut de Mathématiques de Toulouse, UMR 5219 Université de Toulouse/CNRS Université Paul Sabatier, France.
5
Institute of Hematology, University of Perugia, Ospedale S. Maria della Misericordia, Italy.
6
Department of Pathology, Institut Universitaire du Cancer de Toulouse-Oncopole and Centre Hospitalier Universitaire de Toulouse, France.
7
Cancer Research Center of Toulouse (CRCT), UMR1037 Inserm/Université Toulouse III Paul Sabatier, ERL5294 CNRS, Laboratoire d'Excellence Toulouse Cancer (TOUCAN), France bousquetmarina@gmail.com.

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.

PMID:
28679652
PMCID:
PMC5622856
DOI:
10.3324/haematol.2017.171645
[Indexed for MEDLINE]
Free PMC Article

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