RESUMEN
RUNX1 fuses with over 70 different partner genes in hematological neoplasms. While common RUNX1 chimeras have been extensively studied and their prognosis is well established, our current understanding of less common RUNX1 chimeras is limited. Here, we present a case of acute myeloid leukemia (AML) with a rare RUNX1 chimera. Bone marrow cells obtained at diagnosis from a 71-year-old patient diagnosed with AML-M5 were studied using G-banding, fluorescence in situ hybridization, array comparative genomic hybridization, RNA sequencing, PCR, and Sanger sequencing. Combined findings from the abovementioned assays suggested three cytogenetic clones: one with a normal karyotype, one with inv(21)(q21q22), and one with two inv(21)(q21q22). The molecular analysis revealed the fusion of RUNX1 with MIR99AHG (at 21q21.1), further supporting the presence of an inv(21)(q21q22). The present case is the third reported AML harboring a RUNX1::MIR99AHG chimera. Similar to the two previously described AML patients, our case also had an FLT3 aberration.
Asunto(s)
Subunidad alfa 2 del Factor de Unión al Sitio Principal , Leucemia Mieloide Aguda , Proteínas de Fusión Oncogénica , Anciano , Humanos , Masculino , Cromosomas Humanos Par 21/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , MicroARNs/genética , Proteínas de Fusión Oncogénica/genéticaRESUMEN
BACKGROUND: Cellular angiofibroma, a rare benign mesenchymal neoplasm, is classified within the 13q/RB1 family of tumors due to morphological, immunohistochemical, and genetic similarities with spindle cell lipoma. Here, genetic data reveal pathogenetic heterogeneity in cellular angiofibroma. METHODS: Three cellular angiofibromas were studied using G-banding/Karyotyping, array comparative genomic hybridization, RNA sequencing, and direct cycling sequencing. RESULTS: The first tumor carried a del(13)(q12) together with heterozygous loss and minimal expression of the RB1 gene. Tumors two and three displayed chromosome 8 abnormalities associated with chimeras of the pleomorphic adenoma gene 1 (PLAG1). In tumor 2, the cathepsin B (CTSB) fused to PLAG1 (CTSB::PLAG1) while in tumor 3, the mir-99a-let-7c cluster host gene (MIR99AHG) fused to PLAG1 (MIR99AHG::PLAG1), both leading to elevated expression of PLAG1 and insulin growth factor 2. CONCLUSION: This study uncovers two genetic pathways contributing to the pathogenetic heterogeneity within cellular angiofibromas. The first aligns with the 13q/RB1 family of tumors and the second involves PLAG1-chimeras. These findings highlight the diverse genetic landscape of cellular angiofibromas, providing insights into potential diagnostic strategies.