Long non-coding RNA mitophagy and ALK-negative anaplastic lymphoma-associated transcript: a novel regulator of mitophagy in T-cell lymphoma

: Long noncoding RNAs (lncRNAs) are emerging as powerful and versatile regulators of transcriptional programs and distinctive biomarkers of T-cell Lymphoma progression disease. Their role in the aggressive ALK- Anaplastic Large Cell Lymphoma (ALCL) subtype has been only in part elucidated. Starting from our previously identified ALCL-associated lncRNA signature and performing digital gene expression profiling of a retrospective cohort of ALCLs, we defined an 11 lncRNA signature able to discriminate among ALCL subtypes. We selected a not previously characterized lncRNA, MTAAT, with an ALK- ALCL preferential expression, for molecular and functional studies. We demonstrated that lncRNA MTAAT contributes to an aberrant mitochondrial turnover restraining mitophagy and promoting cellular proliferation. Functionally, lncRNA MTAAT acts as a repressor of a set of genes related to mitochondria quality control via chromatin reorganization. Collectively, our work demonstrates the transcriptional role of lncRNA MTAAT in orchestrating a complex transcriptional program sustaining ALK- ALCL progression.