الفهرس 
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Abstract
Background
It has been demonstrated that the insulin-like growth factor type 1 receptor (IGF1R) antisense imprinted non-protein coding RNA (IRAIN), a long non-coding RNA (lncRNA), is downregulated in leukemia cell lines, but its value as a prognostic marker in acute myeloid leukemia (AML) has not yet been thoroughly examined. In this study, we investigated the possibility that the clinical outcome of AML patients is correlated with IRAIN expression.
Although the expression of the long non-coding RNA (lncRNA) insulin-like growth factor type 2 receptor (IGF2R) antisense has been shown to be dysregulated in a number of cancers, it is yet unknown whether acute myeloid leukemia (AML) does the same. It is also unknown how AIRN expression impacts the clinical development of AML.
Subjects & Methods
IRAIN and AIRN expression levels were examined using quantitative real-time polymerase chain reaction (qRT-PCR) in peripheral blood leukocyte samples from 150 patients with AML and 50 healthy controls. The association between gene expression and clinical outcomes in AML patients has been studied.
Results
IRAIN expression was significantly decreased in AML patients when compared to healthy controls (P=0.019). French-American-British (FAB) subtypes of AML could be distinguished by IRAIN expression (P=0.024). Low IRAIN expression status was associated with shorter event-free survival (EFS) in the non-t(15;17) cytogenetically abnormal AML subset (P=0.004). IRAIN downregulation was identified as an independent adverse prognostic marker for complete remission (CR) not only in the in the non-t(15;17) cytogenetically abnormal AML subset (P=0.006) but also in the AML-M4/ M5 subgroup (P=0.033).
We were unable to find any detectable AIRN expression in either AML patients or healthy controls. AIRN appears to have distinctive RNA biology characteristics, particularly a short half-life, which could account for its absence of expression in blood samples from healthy individuals as well as AML patients. AIRN is an imprinted lncRNA that inhibits cis IGF2R expression.
Conclusion
Specifically in non-t(15;17) cytogenetically abnormal AML and M4/M5 AML, aberrantly low IRAIN expression is closely associated with lower CR rates in AML patients, indicating that the determination of IRAIN expression level at diagnosis provides valuable prognostic information, serves as a promising biomarker for evaluating treatment response, and aids in predicting clinical outcome of AML patients.
Future research is required to determine whether AIRN is functional and whether it is directly or indirectly regulated by as-yet unidentified biologic alterations. Additionally, more research is necessary to determine whether AIRN has a direct or indirect role in the pathogenesis and/or maintenance of AML and to determine whether regulating AIRN expression could prevent or slow the development of AML.
Keywords: Acute myeloid leukemia, IGF1R antisense imprinted non protein coding RNA (IRAIN), Antisense of IGF2R non-protein coding RNA (AIRN), Long non-coding RNAs, Prognostic markers.