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 (n = 143), compared to healthy controls (n = 65). Among these, high levels of LINC01268, MALAT1 or GAS5 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 LINC01268 (p = 0.0018), GAS5 (p = 0.0008) or MALAT1 (p = 0.0348) are also associated with a poor overall-survival while high levels of LINC01268 correlate with a shorter leukemia-free-survival. Finally, multivariate analysis demonstrated that the plasma level of LINC01268 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.

The Response to Oxidative Damage Correlates with Driver Mutations and Clinical Outcome in Patients with Myelofibrosis

“…Blood samples were collected via venipuncture in EDTA-containing tubes. Plasma was separated as already described [ 27 ]. Hemolyzed samples were identified by spectrophotometric analyses, measuring the absorbance of hemoglobin at 414 nm using the NanoDrop ND-1000 spectrophotometer (Thermo Fisher Scientific, Waltham, MA, USA).…”

Small molecule targeting long noncoding RNA GAS5 administered intranasally improves neuronal insulin signaling and decreases neuroinflammation in an aged mouse model

“…4 a) show a dose responsive increase in GAS5 and IR levels. Results indicated that 100 nmol was an optimal dose as our goal is to increase GAS5 to physiological levels and not have sustained over-expression which could be detrimental, as observed in certain cancers 34 , 35 . Coronal section of the brain from the 100 nmol NPC86 treated mice were imaged using Keyence BX810 microscope.…”

Long non-coding RNA MALAT1 in hematological malignancies and its clinical applications

“…In the serum of patients with myelofibrosis, MALAT1 was also upregulated compared with healthy controls. [46] Several key molecules have been found to mediate upregulation of MALAT1 expression in hematological malignancies. For example, in MM, Family With Sequence Similarity 46 member C (FAM46C) is one of the most commonly mutated genes; inactivation thereof significantly upregulated MALAT1 in MM cell lines.…”