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Updated: Feb 10, 2026
An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Long intergenic non-coding RNAs have an independent impact on survival in multiple myeloma
Mehmet Kemal Samur1, Stephane Minvielle2,3, Annamaria Gulla1
1Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, 02215, USA.
Abstract:
Although long intergenic non-coding RNAs (lincRNA) role in various cancers is described, their significance in Multiple Myeloma (MM) remains poorly defined. Here we have studied the lincRNA profile and their clinical impact in MM. We performed RNA-seq on MM cells from 308 newly diagnosed and uniformly treated patients, 16 normal plasma cells and utilized RNA-seq data from 532 newly diagnosed patients from CoMMpass study to analyze for lincRNAs. We observed 869 differentially expressed lincRNAs in MM compared to normal plasma cells. We identified 14 lincRNAs associated with PFS and calculated a risk score to stratify patients. The median PFS between high vs low-risk groups was 17 months vs not-reached (NR); and OS 30 months vs NR, respectively (p < 0.0001 for both). In the independent validation dataset between high and low-risk groups, PFS was 27 vs 42 months (HR 2.06 [1.44-2.96]; p < 0.0005); and 4-year OS 62% vs 86% (HR 2.76 [1.51-5.05]; p < 0.0005) confirming significant clinical relevance of lincRNA in MM. Importantly, lincRNA signature was able to further identify patients with significant differential outcomes within each low and high-risk categories identified using standard risk categorization including cytogenetic/FISH, ISS, and MRD negative or positive. Our results suggest that lincRNAs have an independent effect on MM outcome and provide a rationale to evaluate its molecular and biological impact.
Insights
Long intergenic non-coding RNAs (lincRNAs) significantly impact Multiple Myeloma (MM) patient outcomes. A novel lincRNA signature accurately predicts progression-free survival and overall survival, improving risk stratification beyond standard methods.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- The role of long intergenic non-coding RNAs (lincRNAs) in cancer is recognized, but their specific significance in Multiple Myeloma (MM) is not well-defined.
- Understanding lincRNA profiles in MM is crucial for identifying novel prognostic markers.
Purpose of the Study:
- To investigate the lincRNA expression profile in Multiple Myeloma (MM) patients.
- To determine the clinical impact and prognostic value of lincRNAs in MM.
- To develop a lincRNA-based risk score for patient stratification.
Main Methods:
- RNA sequencing (RNA-seq) was performed on MM cells from 308 newly diagnosed patients and 16 normal plasma cells.
- RNA-seq data from 532 MM patients in the CoMMpass study were utilized for analysis.
- A risk score was calculated based on 14 identified lincRNAs associated with progression-free survival (PFS).
Main Results:
- 869 differentially expressed lincRNAs were identified in MM compared to normal plasma cells.
- A 14-lincRNA signature significantly stratified patients into high-risk and low-risk groups, with distinct median PFS (17 months vs. not reached) and overall survival (OS) (30 months vs. not reached).
- Validation in an independent dataset confirmed the prognostic value, showing significant differences in PFS and 4-year OS between risk groups (PFS: 27 vs. 42 months; OS: 62% vs. 86%).
- The lincRNA signature improved risk stratification within established categories (cytogenetics, ISS, MRD status).
Conclusions:
- lincRNAs play a significant and independent role in determining Multiple Myeloma (MM) patient outcomes.
- A novel lincRNA-based risk score offers valuable prognostic information, enhancing current risk stratification strategies.
- These findings provide a strong rationale for further investigation into the molecular and biological functions of lincRNAs in MM pathogenesis and progression.
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