Expression and prognostic impact of lncRNAs in acute myeloid leukemia.

Published

Journal Article

Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides, located within the intergenic stretches or overlapping antisense transcripts of protein coding genes. 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 y) 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 patients with CN-AML was used to validate the outcome scores using RNA sequencing. Distinctive lncRNA profiles were found associated with selected mutations, such as internal tandem duplications in the FLT3 gene (FLT3-ITD) and mutations in the NPM1, CEBPA, IDH2, ASXL1, and RUNX1 genes. Using the lncRNAs most associated with event-free survival in a training cohort of 148 older patients with CN-AML, we derived a lncRNA score composed of 48 lncRNAs. Patients with an unfavorable compared with favorable lncRNA score had a lower complete response (CR) rate [P < 0.001, odds ratio = 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. 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.

Full Text

Duke Authors

Cited Authors

  • Garzon, R; Volinia, S; Papaioannou, D; Nicolet, D; Kohlschmidt, J; Yan, PS; Mrózek, K; Bucci, D; Carroll, AJ; Baer, MR; Wetzler, M; Carter, TH; Powell, BL; Kolitz, JE; Moore, JO; Eisfeld, A-K; Blachly, JS; Blum, W; Caligiuri, MA; Stone, RM; Marcucci, G; Croce, CM; Byrd, JC; Bloomfield, CD

Published Date

  • December 15, 2014

Published In

Volume / Issue

  • 111 / 52

Start / End Page

  • 18679 - 18684

PubMed ID

  • 25512507

Pubmed Central ID

  • 25512507

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.1422050112

Language

  • eng