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

The cover for issue 1 of Oncotarget features Figure 7, "KEGG pathways," by Tschumper, et al.

Alterations in long non-coding RNA 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.

Thus, our study reveals differentially expressed lnc RNAs in progressive early stage CLL requiring therapy versus indolent early Rai stage UM CLL.

"Chronic lymphocytic leukemia remains a clinically heterogeneous disease despite recent advances in disease classification centered upon cellular and molecular markers."

Lnc RNAs are transcribed RNA molecules greater than 200 nucleotides long and have been traditionally defined as having no open reading frame, although many lnc RNAs associate with ribosomes and may encode short peptides.

Figure 7: KEGG pathways. Enriched pathways in (A) up-regulated transcripts and (B) down-regulated transcripts differentially expressed in PD vs ID CLL.

Studies of lnc RNA expression in B cell development indicate a role for lnc RNAs in the pathogenesis and progression of B cell malignancies.

Indeed, there is evidence that lnc RNAs can associate with clinical features in human acute and chronic leukemias allowing for discrimination of disease subtypes and clinical outcomes.

In this study, we used a microarray based approach to analyze the lnc RNA and mRNA expression profiles of Rai 0/I UM CLL patients with progressive disease requiring therapy 2 years) compared to those with more stable, indolent disease.

Moreover, the data provide a crucial foundation for future studies investigating the utility of any of these lnc RNAs to serve as biomarkers that may allow earlier prediction of disease progression.

"The IGHV mutation status in CLL has long been used as marker of disease progression with much more unfavorable disease kinetics for CLL clones expressing an UM IGHV. In this study we show for the first time that even within a very specific clinical and prognostic subset of CLL, i.e., Rai 0/I UM IGHV CLL, both well annotated and novel lnc RNAs are dysregulated and may be playing a role by altering expression of known associated or nearby genes involved in CLL pathogenesis."

Full text - https://doi.org/10.18632/oncotarget.26538

Correspondence to - Diane F. Jelinek - jelinek.diane@mayo.edu

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