Prognostic value and biologic implications of long coding RNAs in CN-AML patients

Long Non-Coding RNAs (IncRNAs) are a class of RNA molecules that are longer than 200 nucleotides with no protein coding potential. IncRNAs has been shown to contribute to the initiation, maintenance, and development of Acute Myeloid Leukemia (AML).¹ However, the prognostic importance of IncRNAs in the clinical outcomes of AML patients has not been extensively explored.

Dimitrios Papaioannou from The Ohio State University, Comprehensive Cancer Center, Columbus, USA, and colleagues investigated the prognostic and biological significance of IncRNAs in Cytogenetically Normal AML (CN-AML). The results of the study were published ahead of print in Haematologica on 4^th May 2017.

In this study, whole transcriptome sequencing was used to characterize the IncRNAs profiles of 377 pre-treatment bone marrow or blood samples from young adults patients with de novo CN-AML (17–59 years) who received intensive induction therapy on the Cancer and Leukemia Group B (CALCGB)/Alliance for Clinical Trials in Oncology trials. Patients samples were split into two cohorts, training (n = 263) and validation (n = 114).

The key results of the study were:

• Using exploratory analysis on the training cohort, twenty-four IncRNAs were found to be associated with Event Free Survival (EFS); P < 10^-6
• Linear combination of the weighted expression values of the identified twenty-four IncRNA transcripts generated a prognostic score which divided patients into either favorable (low) or unfavorable (high) IncRNA score
• 5-year Disease Free Survival (DFS) in patients with favorable and unfavorable IncRNA scores in the validation cohort; 51% vs 17%, P < 0.001
• 5-year Overall Survival (OS) in patients with favorable and unfavorable IncRNA scores in the validation cohort; 52% vs 26%, P = 0.002
• 5-year EFS in patients with favorable and unfavorable IncRNA scores in the validation cohort; 46% vs 16%, P < 0.001
• Favorable IncRNA was an independent prognostic marker for longer DFS (P = 0.01) and EFS (P = 0.002) and a trend towards longer OS (P = 0.06)
• Distinct IncRNA signatures were associated with NPM1 mutations, FLT3-ITD mutations, and double mutated CEBPA
• mRNA and microRNA (miRNA) expression transcripts correlated with unfavorable IncRNA score
• Genes involved in oncogenesis, lymphocyte/leukocyte activation, inflammation, and apoptosis were enriched in patients with unfavorable IncRNA score

In summary, “IncRNA provides a meaningful prognostic information in young adults with CN-AML”. Furthermore, “expression of prognostic IncRNAs may regulate distinct molecular pathways in CN-AML”.