Oncotarget

Research Papers:

Role of long non-coding RNAs in disease progression of early stage unmutated chronic lymphocytic leukemia

Renee C. Tschumper, Tait D. Shanafelt, Neil E. Kay and Diane F. Jelinek _

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Abstract

Renee C. Tschumper1, Tait D. Shanafelt3, Neil E. Kay4 and Diane F. Jelinek2,4

1Department of Immunology, Mayo Clinic, Rochester, MN, USA

2Department of Immunology, Mayo Clinic, Scottsdale, AZ, USA

3Department of Hematology/Oncology, Stanford University, Stanford, CA, USA

4Department of Internal Medicine, Division of Hematology, Mayo Clinic, Rochester, MN, USA

correspondence to:

Diane F. Jelinek, email: jelinek.diane@mayo.edu

Keywords: long non-coding RNA; chronic lymphocytic leukemia; unmutated immunoglobulin heavy chain variable region; progression; early Rai stage

Received: October 27, 2018    Accepted: December 12, 2018    Published: January 01, 2019

ABSTRACT

Predicting disease progression in chronic lymphocytic leukemia (CLL) remains challenging particularly in patients with Rai Stage 0/I disease that have an unmutated immunoglobulin heavy chain variable region (UM IGHV). Even though patients with UM IGHV have a poor prognosis and generally require earlier treatment, not all UM IGHV patients experience more rapid disease progression with some remaining treatment free for many years. This observation suggests biologic characteristics other than known prognostic factors influence disease progression. Alterations in long non-coding RNA (lncRNA) expression levels have been implicated in diagnosis and prognosis of various cancers, however, their role in disease progression of early Rai stage UM CLL is unknown. Here we use microarray analysis to compare lncRNA and mRNA profiles of Rai 0/I UM IGHV patients who progressed in <2 years relative to patients who had not progressed for >5 years. Over 1,300 lncRNAs and 940 mRNAs were differentially expressed (fold change ≥ 2.0; p-value ≤ 0.05). Of interest, the differentially expressed lncRNAs T204050, NR_002947, and uc.436+, have known associated genes that have been linked to CLL. Thus, our study reveals differentially expressed lncRNAs in progressive early stage CLL requiring therapy versus indolent early Rai stage UM CLL. These lncRNAs have the potential to impact relevant biological processes and pathways that influence clinical outcome in CLL.


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