RESUMO
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.
Assuntos
Linfoma Anaplásico de Células Grandes , Linfoma de Células T Periférico , RNA Longo não Codificante , Humanos , Receptores Proteína Tirosina Quinases/genética , Quinase do Linfoma Anaplásico/genética , RNA Longo não Codificante/genética , Mitofagia/genética , Estudos Retrospectivos , Linfoma Anaplásico de Células Grandes/patologiaRESUMO
Lymphoma patients are at high risk of cardiovascular events due to anthracycline cardiotoxicity and, in rare cases, related to heart infiltration. The presence of cardiac masses adds further complexity to the management of lymphoma patients beyond myocardial chemotherapy-related toxicity, given possible unpredictable acute complications such as arrhythmias, atrioventricular block, myocardial ischemia, pericardial effusion and cardiac tamponade. Here we describe the clinical presentation and successful multidisciplinary management of diffuse large B-cell lymphoma with multifocal cardiac involvement identified by total body 18FDG positron emission tomography performed at disease staging.