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Haematologica. 2017 Aug;102(8):1391-1400. doi: 10.3324/haematol.2017.166215. Epub 2017 May 4.

Prognostic and biologic significance of long non-coding RNA profiling in younger adults with cytogenetically normal acute myeloid leukemia.

Author information

1
The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
2
The Alliance for Clinical Trials in Oncology Statistics and Data Center, Mayo Clinic, Rochester, MN, USA.
3
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Italy.
4
Department of Physics, Department of Chemistry & Biochemistry, Division of Hematology, Department of Internal Medicine, Center for RNA Biology, The Ohio State University, Columbus, OH, USA.
5
Department of Genetics, University of Alabama at Birmingham, AL, USA.
6
The Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC, USA.
7
Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.
8
Hofstra North Shore-Long Island Jewish School of Medicine, Lake Success, NY, USA.
9
Roswell Park Cancer Institute, Buffalo, NY, USA.
10
Dana-Farber Cancer Institute, Harvard University, Boston, MA, USA.
11
The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA ramiro.garzon@osumc.edu clara.bloomfield@osumc.edu.

Abstract

Long non-coding ribonucleic acids (RNAs) are a novel class of RNA molecules, which are increasingly recognized as important molecular players in solid and hematologic malignancies. Herein we investigated whether long non-coding RNA expression is associated with clinical and molecular features, as well as outcome of younger adults (aged <60 years) with de novo cytogenetically normal acute myeloid leukemia. Whole transcriptome profiling was performed in a training (n=263) and a validation set (n=114). Using the training set, we identified 24 long non-coding RNAs associated with event-free survival. Linear combination of the weighted expression values of these transcripts yielded a prognostic score. In the validation set, patients with high scores had shorter disease-free (P<0.001), overall (P=0.002) and event-free survival (P<0.001) than patients with low scores. In multivariable analyses, long non-coding RNA score status was an independent prognostic marker for disease-free (P=0.01) and event-free survival (P=0.002), and showed a trend for overall survival (P=0.06). Among multiple molecular alterations tested, which are prognostic in cytogenetically normal acute myeloid leukemia, only double CEBPA mutations, NPM1 mutations and FLT3-ITD associated with distinct long non-coding RNA signatures. Correlation of the long non-coding RNA scores with messenger RNA and microRNA expression identified enrichment of genes involved in lymphocyte/leukocyte activation, inflammation and apoptosis in patients with high scores. We conclude that long non-coding RNA profiling provides meaningful prognostic information in younger adults with cytogenetically normal acute myeloid leukemia. In addition, expression of prognostic long non-coding RNAs associates with oncogenic molecular pathways in this disease. clinicaltrials.gov Identifier: 00048958 (CALGB-8461), 00899223 (CALGB-9665), and 00900224 (CALGB-20202).

PMID:
28473620
PMCID:
PMC5541873
DOI:
10.3324/haematol.2017.166215
[Indexed for MEDLINE]
Free PMC Article

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