Expression and prognostic relevance of long noncoding RNAs CRNDE and AOX2P in adult acute myeloid leukemia

Abstract

Introduction Several long noncoding RNAs (lncRNAs) have been demonstrated to play a critical role in the tumorigenesis of acute myeloid leukemia (AML), and altered expression of certain lncRNAs has been recognized as a potential prognostic marker in AML patients. Here, we sought to determine whether the expression of the lncRNA colorectal neoplasia differentially expressed (CRNDE) and aldehyde oxidase 2 pseudogene (AOX2P) is associated with clinicopathological features and clinical outcome of patients with AML. Methods CRNDE and AOX2P expression levels were measured in diagnostic blood samples from 200 adult patients with de novo AML, along with 50 healthy control blood samples, using quantitative real‐time polymerase chain reaction (qRT‐PCR). The association of CRNDE and AOX2P expression with the clinicopathological characteristics and outcome of AML patients was analyzed. Results Upregulated CRNDE expression was independently associated with lower complete remission (CR) rates in the whole cohort of AML (P < .001). AOX2P overexpression was identified as an independent adverse prognostic marker for CR in the CN‐AML (P = .009) and non‐t (15;17) AML (P < .001) subgroups. Patients with high CRNDE expression had a significantly shorter event‐free survival (EFS, whole cohort of AML: P = .017; CN‐AML: P = .001; non‐t (15;17) AML: P = .006) and inferior overall survival (OS, whole cohort of AML: P = .002; t(15;17) AML: P = .001) than those with low CRNDE expression. EFS and OS did not differ significantly between patients with high AOX2P expression and those with low expression. Conclusion Aberrantly upregulated CRNDE expression and, to a lesser extent, AOX2P overexpression, are associated with poor prognosis in AML patients, suggesting that the determination of CRNDE and, perhaps, AOX2P, expression level at diagnosis provides valuable prognostic information, allows refinement of risk stratification, and helps clinical decision‐making in AML.

Development and validation of a promising 5-gene prognostic model for pediatric acute myeloid leukemia

“…Especially, Colorectal neoplasia differentially expressed (CRNDE) is a well-known long non-coding RNA which was considered to play crucial roles in the development of multiple cancers [ 35 ]. Moreover, it was highly expressed in AML [ 35 , 36 ], displayed functional roles in AML proliferation [ 37 ] and indicated by previous analyses to have prognostic value in AML [ 36 , 38 ]. Explorations focusing on the detailed mechanisms of CRNDE in P-AML pathology might help to identify a promising therapeutic strategy.…”

Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia

“…In AML CRNDE has an oncogenic function. High expression of CRNDE is associated with lower CR and shorter disease-free survival (DFS) and over-all survival (OS), and therefore can be used as a molecular marker predicting inferior outcome [103,104]. Especially high expression level was detected among APL and NPM1-mutated AML patients, promoting proliferation of leukemic cells and blocking myeloid differentiation.…”

Diverse functions of long noncoding RNAs in acute myeloid leukemia: emerging roles in pathophysiology, prognosis, and treatment resistance

“…However, the precise functional roles of CRNDE in NPM1 mutated AML remains unclear. Recently, Hola et al conducted qRT-PCR based expression analysis of CRNDE from the diagnostic blood samples of 200 de novo adult AML patients compared to 50 healthy control samples, which revealed that upregulation of CRNDE was an adverse independent prognostic marker for complete remission in CN-AML patients [29].…”