Increased Plasma Levels of lncRNAs LINC01268, GAS5 and MALAT1 Correlate with Negative Prognostic Factors in Myelofibrosis

Abstract

Long non-coding RNAs (lncRNAs) have been recently described as key mediators in the development of hematological malignancies. In the last years, circulating lncRNAs have been proposed as a new class of non-invasive biomarkers for cancer diagnosis and prognosis and to predict treatment response. The present study is aimed to investigate the potential of circulating lncRNAs as non-invasive prognostic biomarkers in myelofibrosis (MF), the most severe among Philadelphia-negative myeloproliferative neoplasms. We detected increased levels of seven circulating lncRNAs in plasma samples of MF patients (<i>n</i> = 143), compared to healthy controls (<i>n</i> = 65). Among these, high levels of <i>LINC01268</i>, <i>MALAT1</i> or <i>GAS5</i> correlate with detrimental clinical variables, such as high count of leukocytes and CD34+ cells, severe grade of bone marrow fibrosis and presence of splenomegaly. Strikingly, high plasma levels of <i>LINC01268 (</i><i>p</i> = 0.0018)<i>, GAS5</i> (<i>p</i> = 0.0008) or <i>MALAT1</i> (<i>p</i> = 0.0348) are also associated with a poor overall-survival while high levels of <i>LINC01268</i> correlate with a shorter leukemia-free-survival. Finally, multivariate analysis demonstrated that the plasma level of <i>LINC01268</i> is an independent prognostic variable, suggesting that, if confirmed in future in an independent patients' cohort, it could be used for further studies to design an updated classification model for MF patients.