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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.

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The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
The Alliance for Clinical Trials in Oncology Statistics and Data Center, Mayo Clinic, Rochester, MN, USA.
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Italy.
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.
Department of Genetics, University of Alabama at Birmingham, AL, USA.
The Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC, USA.
Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.
Hofstra North Shore-Long Island Jewish School of Medicine, Lake Success, NY, USA.
Roswell Park Cancer Institute, Buffalo, NY, USA.
Dana-Farber Cancer Institute, Harvard University, Boston, MA, USA.
The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA


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. Identifier: 00048958 (CALGB-8461), 00899223 (CALGB-9665), and 00900224 (CALGB-20202).

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