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

TitleLong non-coding RNA mitophagy and ALK-negative anaplastic lymphoma-associated transcript: a novel regulator of mitophagy in T-cell lymphoma.
Publication TypeJournal Article
Year of Publication2023
AuthorsMularoni V, Donati B, Tameni A, Manicardi V, Reggiani F, Sauta E, Zanelli M, Tigano M, Vitale E, Torricelli F, Ascani S, Martino G, Inghirami G, Sanguedolce F, Ruffini A, Bavieri A, Luminari S, Pizzi M, Tos APaolo Dei, Fesce C, Neri A, Ciarrocchi A, Fragliasso V
JournalHaematologica
Volume108
Issue12
Pagination3333-3346
Date Published2023 Dec 01
ISSN1592-8721
KeywordsAnaplastic Lymphoma Kinase, Humans, Lymphoma, Large-Cell, Anaplastic, Lymphoma, T-Cell, Peripheral, Mitophagy, Receptor Protein-Tyrosine Kinases, Retrospective Studies, RNA, Long Noncoding
Abstract

Long non-coding RNA (lncRNA) are emerging as powerful and versatile regulators of transcriptional programs and distinctive biomarkers of progression of T-cell lymphoma. Their role in the aggressive anaplastic lymphoma kinase-negative (ALK-) subtype of anaplastic large cell lymphoma (ALCL) has been elucidated only in part. Starting from our previously identified ALCL-associated lncRNA signature and performing digital gene expression profiling of a retrospective cohort of ALCL, we defined an 11 lncRNA signature able to discriminate among ALCL subtypes. We selected a not previously characterized lncRNA, MTAAT, with preferential expression in ALK- ALCL, 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 mitochondrial quality control via chromatin reorganization. Collectively, our work demonstrates the transcriptional role of lncRNA MTAAT in orchestrating a complex transcriptional program sustaining the progression of ALK- ALCL.

DOI10.3324/haematol.2022.282552
Alternate JournalHaematologica
PubMed ID37381763
PubMed Central IDPMC10690924
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