Expression Profiles of Long Non-Coding RNA GAS5 and MicroRNA-222 in Younger AML Patients.

Djordje Pavlovic,Nada Suvajdzic Vukovic,Sonja Pavlovic,Branka Zukic,Vladimir Gasic,Zlatko Pravdic,Natasa Tosic

doi:10.3390/diagnostics12010086

Abstract

Acute myeloid leukemia (AML) is a heterogeneous malignant disease both on clinical and genetic levels. AML has poor prognosis and, therefore, there is a constant need to find new prognostic markers, as well as markers that can be used as targets for innovative therapeutics. Recently, the search for new biomarkers has turned researchers’ attention towards non-coding RNAs, especially long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs). We investigated the expression level of growth arrest-specific transcript 5 (GAS5) lncRNA in 94 younger AML patients, and also the expression level of miR-222 in a cohort of 39 AML patients with normal karyotype (AML-NK), in order to examine their prognostic potential. Our results showed that GAS5 expression level in AML patients was lower compared to healthy controls. Lower GAS5 expression on diagnosis was related to an adverse prognosis. In the AML-NK group patients had higher expression of miR-222 compared to healthy controls. A synergistic effect of GAS5low/miR-222high status on disease prognosis was not established. This is the first study focused on examining the GAS5 and miR-222 expression pattern in AML patients. Its initial findings indicate the need for further investigation of these two non-coding RNAs, their potential roles in leukemogenesis, and the prognosis of AML patients.

Highlights

Acute myeloid leukemia (AML) is a hematological malignancy that is characterized by the uncontrolled proliferation and impaired differentiation of early myeloid cells leading to accumulation of immature blast cells in the bone marrow and peripheral blood, resulting in hematopoietic failure
Analyzing the association of growth arrest-specific transcript 5 (GAS5) expression level with clinical characteristic of de novo AML patients, we found that GAS5low patients had significantly higher Lactate Dehydrogenase (LDH) levels in comparison to GAS5high patients (p = 0.04)
When we analyzed the prognostic impact of GAS5 expression among de novo AML patients we found that low GAS5 expression is predominantly detected among patients with an adverse prognosis

Summary

Introduction

Acute myeloid leukemia (AML) is a hematological malignancy that is characterized by the uncontrolled proliferation and impaired differentiation of early myeloid cells leading to accumulation of immature blast cells in the bone marrow and peripheral blood, resulting in hematopoietic failure. AML is the most common acute leukemia in adults, accounting for about 80% of all cases It is a neoplastic disorder with very poor prognosis, despite the progress made towards discovering the exact etiology of AML. This is due to the fact that the initial treatment protocol is still based on the classification of the patients into risk groups based on the pretreatment karyotype analysis. Nearly half of the patients do not have any detectable cytogenetic changes. They are referred to as AML with normal karyotype (AML-NK) patients, categorized into the intermediate risk group. There is a constant need for discovery of new molecular markers that would lead towards more precise risk stratification and efficient personalized therapeutic protocols

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