Journal of Blood Disorders & Transfusion

Expression and prognostic impact of long non-coding RNAs in acute myeloid leukemia

3^rd International Conference on Hematology & Blood Disorders

November 02-04, 2015 Atlanta, USA

Ramiro Garzon

The Ohio State University, USA

Posters-Accepted Abstracts: J Blood Disord Transfus

Abstract:

Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides located within the intergenic stretches or overlapping antisense transcripts of protein coding genes. The lncRNAs are involved in numerous biological roles including imprinting, epigenetic regulation, apoptosis and cell-cycle. To determine whether lncRNAs are associated with clinical features and recurrent mutations in older patients (aged �?�60 years) with cytogenetically normal (CN) acute myeloid leukemia (AML), we evaluated lncRNA expression in 148 untreated older CN-AML cases using a custom microarray platform. An independent set of 71 untreated older CN-AML patients was used to validate the outcome scores using RNA-seq. Distinctive lncRNA profiles were found associated with selected mutations such as FLT3 internal tandem duplications (FLT3-ITD) and NPM1, CEBPA, IDH2, ASXL1 and RUNX1 mutations. Using the lncRNAs most associated with event-free survival in a training cohort of 148 older CN-AML patients we derived lncRNA score comprised of 48 lncRNAs. Patients with an unfavorable compared with favorable lncRNA score had a lower complete response (CR) rate [P<0.001, odds ratio (OR)=0.14, 54% vs. 89%], shorter disease-free survival (DFS) [P<0.001, hazard ratio (HR)=2.88] and overall survival (OS) (P<0.001, HR=2.95). The validation set analyses confirmed these results (CR, P=0.03; DFS, P=0.009; OS, P=0.009). Multivariable analyses for CR, DFS and OS identified the lncRNA score as an independent marker for outcome. The functional impact of several lncRNAs was investigated and data will be presented at the meeting. In conclusion, lncRNA expression in AML is closely associated with recurrent mutations. A small subset of lncRNAs is correlated strongly with treatment response and survival.

Biography :

Email: ramiro.garzon@osumc.edu