Abstract
Non-coding RNAs (ncRNAs) are essential regulators of gene expression. In recent years, it has become more and more evident that the different classes of ncRNAs, such as micro RNAs, long non-coding RNAs and circular RNAs are organized in tightly controlled networks. It has been suggested that deregulation of these networks can lead to disease. Several studies show a contribution of these so-called competing-endogenous RNA networks in various cancer entities. In this review, we highlight the involvement of ncRNA networks in anaplastic-large cell lymphoma (ALCL), a T-cell neoplasia. A majority of ALCL cases harbor the molecular hallmark of this disease, a fusion of the anaplastic lymphoma kinase (ALK) gene with the nucleophosmin (NPM, NPM1) gene leading to a permanently active kinase that promotes the malignant phenotype. We have focused especially on ncRNAs that are regulated by the NPM-ALK fusion gene and illustrate how their deregulation contributes to the pathogenesis of ALCL. Lastly, we summarize the findings and point out potential therapeutic implications.
Highlights
Anaplastic large cell lymphoma (ALCL) is a rare and aggressive peripheral T-cell non-Hodgkin lymphoma (NHL), belonging to the group of CD30-positive lymphoproliferative disorders
Anaplastic Lymphoma Kinase (ALK) fusions were first identified in inflammatory myofibroblastic tumors, and in 2007 the echinoderm microtubule associated protein like4 (EML4)-ALK fusion protein was reported in non-small cell lung cancer (NSCLC) [10]
Considering the amount of known micro RNAs (miRNA) genes and microRNA response elements (MREs) harboring transcripts in the human transcriptome, this model of competing endogenous RNAs in a self-organized context adds a new layer of complexity to post-transcriptional and translational regulation mediated by microRNAs as a hub for RNA crosstalk
Summary
Anaplastic large cell lymphoma (ALCL) is a rare and aggressive peripheral T-cell non-Hodgkin lymphoma (NHL), belonging to the group of CD30-positive lymphoproliferative disorders. Whereas most clinical results regarding ALK inhibitors come from patients with EML4-ALK-positive NSCLC, it is clear that ALK inhibition is a potentially effective treatment strategy in all ALK-expressing malignancies evaluated so far and especially so in relapsed ALK-positive ALCL. The clinical trial (NCT00939770) of crizotinib in children with refractory ALK-positive ALCL, or with solid tumors, resulted in a complete response in 8 out of 9 patients with ALK-positive ALCL, exceeding the response rate in the other ALK-expressing malignancies [13]. Non-coding RNAs contribute to ALCL pathology in different ways and are often responsible for drug resistance They can be identified as relevant therapeutic targets, but might be promising biomarkers for the screening of therapeutic resistance of ALK-positive ALCL
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
