RESUMEN
Adenosine-to-inosine RNA editing, which is catalyzed by adenosine deaminases acting on RNA (ADAR) family of enzymes, ADAR1 and ADAR2, has been shown to contribute to multiple cancers. However, other than the chronic myeloid leukemia blast crisis, relatively little is known about its role in other types of hematological malignancies. Here, we found that ADAR2, but not ADAR1 and ADAR3, was specifically downregulated in the core-binding factor (CBF) acute myeloid leukemia (AML) with t(8;21) or inv(16) translocations. In t(8;21) AML, RUNX1-driven transcription of ADAR2 was repressed by the RUNX1-ETO additional exon 9a fusion protein in a dominant-negative manner. Further functional studies confirmed that ADAR2 could suppress leukemogenesis specifically in t(8;21) and inv16 AML cells dependent on its RNA editing capability. Expression of 2 exemplary ADAR2-regulated RNA editing targets coatomer subunit α and component of oligomeric Golgi complex 3 inhibits the clonogenic growth of human t(8;21) AML cells. Our findings support a hitherto, unappreciated mechanism leading to ADAR2 dysregulation in CBF AML and highlight the functional relevance of loss of ADAR2-mediated RNA editing to CBF AML.
Asunto(s)
Factores de Unión al Sitio Principal , Leucemia Mieloide Aguda , Humanos , Regulación hacia Abajo , Factores de Unión al Sitio Principal/metabolismo , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , Edición de ARN , Adenosina Desaminasa/genética , Adenosina Desaminasa/metabolismo , Leucemia Mieloide Aguda/genética , Adenosina/metabolismoRESUMEN
BACKGROUND: Penile schwannoma is a rare tumor. They commonly present as an asymptomatic, painless and slow growing mass. Other presentations include sexual dysfunction, most commonly dyspareunia, followed by erectile dysfunction, abnormal penile curvature or pain with ejaculation. CASE PRESENTATION: A 26-year-old male presented atypically with painful nocturnal penile tumescence, along with multiple nodules over the dorsal penis. Excision of multiple penile tumors under general anaesthesia was performed and histopathologic examination revealed benign schwannoma. CONCLUSION: Our hypothesis is that the schwannoma lies along the axis of the dorsal penile nerve, and compression of this nerve occurs during his erection causing pain. However, there are limited presentations of painful erections in penile schwannomas, and we hope that future studies can help confirm this theory.
ABSTRAITE: CONTEXTE: Le schwannome pénien est. une tumeur rare. Il se présente généralement comme une masse asymptomatique, indolore et à croissance lente. D'autres présentations incluent la dysfonction sexuelle, le plus souvent la dyspareunie, suivie de la dysfonction érectile, de la courbure anormale du pénis ou de la douleur à l'éjaculation. PRéSENTATION DU CAS: Un homme de 26 ans s'est. présenté de façon atypique avec une tumescence pénienne nocturne douloureuse, ainsi que de multiples nodules sur la face dorsale du pénis. L'excision de plusieurs tumeurs du pénis a été réalisée sous anesthésie générale et un examen histopathologique a révélé un schwannome bénin. CONCLUSION: Notre hypothèse est. que le schwannome se trouve localisé le long de l'axe du nerf pénien dorsal, et que la compression de ce nerf se produit pendant l'érection, constituant la source des douleurs. Cependant, il existe peu de présentations d'érections douloureuses dans les schwannomes péniens, et nous espérons que de futures études pourront aider à confirmer cette théorie.