Acute Myeloid Leukemia (AML) is the most common form of leukemia in adults with an incidence of 4.3 per 100,000 cases per year. Historically, the identification of genetic alterations in AML focused on protein-coding genes to provide biomarkers and to understand the molecular complexity of AML. Despite these findings and because of the heterogeneity of this disease, questions as to the molecular mechanisms underlying AML development and progression remained unsolved. Recently, transcriptome-wide profiling approaches have uncovered a large family of long noncoding RNAs (lncRNAs). Larger than 200 nucleotides and with no apparent protein coding potential, lncRNAs could unveil a new set of players in AML development. Originally considered as dark matter, lncRNAs have critical roles to play in the different steps of gene expression and thus affect cellular homeostasis including proliferation, survival, differentiation, migration or genomic stability. Consequently, lncRNAs are found to be differentially expressed in tumors, notably in AML, and linked to the transformation of healthy cells into leukemic cells. In this review, we aim to summarize the knowledge concerning lncRNAs functions and implications in AML, with a particular emphasis on their prognostic and therapeutic potential.Cancers 2019, 11, 1638 2 of 24 highlighted recently but are steadily on the increase. Herein, we review the current understanding of lncRNAs deregulation in AML with an emphasis on their putative therapeutic potential.
Background on lncRNAsArbitrary defined as transcripts of over 200 nucleotides without coding potential, lncRNAs were originally considered as dark matter due to their low expression and poor conservation across species compared to their messenger RNAs counterparts [13][14][15][16]. However, lncRNAs are tightly controlled and exhibit higher tissue and development specific expression than proteins-including lineage determining transcription factors-which support their biological functions [17,18]. Mostly transcribed by RNA Polymerase II, lncRNAs mimic mRNAs in their biogenesis and regulation: most of them are capped, polyadenylated, and spliced via canonical genomic splice site motifs [16]. Their transcription is also regulated by chromatin modifying complexes and specific transcription factors. Nevertheless, we also observe diversity with some non-polyadenylated or unspliced lncRNAs, lncRNAs transcribed by RNA Polymerase III [19,20] and snoRNA-related lncRNAs (sno-lncRNAs) expressed from introns via the snoRNP machinery [21].Because of their heterogeneity, much debate remains to find the best classification system for lncRNAs that are currently defined according to their genomic location. Indeed, lncRNAs can be divided into sense [22] or antisense [23] lncRNAs when the lncRNA sequence overlaps with the sense or antisense strand of a protein coding gene, respectively. They can also be defined as intronic lncRNA when it is derived entirely from an intron of another gene, as bidirectional when the transcription of the lncRNA is i...