Leukemia subgroups can be characterized by a specific lncRNA expression pattern

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy of immature developing precursor T-cells and can be classified into different molecular genetic subgroups based on the aberrant activation of particular transcription factor oncogenes. In addition, these distinct molecular entities display specific gene expression signatures and can be linked to certain stages of T-cell development. Most genetic subtypes of human T-ALL are named after the transcription factor oncogene that is predominantly altered in these hematological tumors, that is, TAL/LMO, TLX1 (HOX11), TLX3 (HOX11L2) or HOXA. However, immature T-ALLs, which generally lack a unifying molecular genetic alteration, are also considered as a separate T-ALL entity with putative clinical relevance.

Long noncoding RNAs (lncRNAs) are a novel class of untranslated RNAs that are at least 200 nucleotides in size and are implicated in a wide variety of cellular functions and specific developmental processes. Notably, recent studies have shown that lncRNAs can drive tumor development and, in the context of T-ALL, it has been described that NOTCH1 regulates the expression of several lncRNAs. One interesting example is LUNAR1, which enhances the expression of IGF1R, leading to sustained IGF1 signaling. Thus far, lncRNAs remained unexplored as genetic markers for distinct T-ALL subtypes.

In this study, researchers from Ghent University defined the pattern of lncRNA expression in different molecular genetic subtypes of human T-ALL. Integration of these signatures with lncRNA expression in T-ALL cell lines and specific stages of normal human T-cell development provides a resource for the identification of oncogenic or tumor suppressive lncRNAs in the context of T-cell transformation.

T-ALL subgroups can be characterized by a specific lncRNA expression pattern


(a) Heatmaps showing the top 50 most differentially expressed mRNAs (left) and lncRNAs (right) for each subgroup (adjusted P-value<0.05). (b) Gene set enrichment analysis using the top 50 lncRNAs upregulated in the respective genetic T-ALL subgroups as gene sets within a panel of T-ALL cell lines. (c) For each subgroup, one lncRNA from the core enrichment of the cell lines is visualized with RNA sequencing and H3K27ac ChIP-sequencing tracks for LOUCY, ALL-SIL and JURKAT.

Wallaert A, Durinck K, Van Loocke W, Van de Walle I, Matthijssens F, Volders PJ, Avila Cobos F, Rombaut D, Rondou P, Mestdagh P, Vandesompele J, Poppe B, Taghon T, Soulier J, Van Vlierberghe P, Speleman F. (2016) Long noncoding RNA signatures define oncogenic subtypes in T-cell acute lymphoblastic leukemia. Leukemia [Epub ahead of print]. [abstract]

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