<p>A translational gap exists in Burkitt leukemia (B-AL) and Burkitt lymphoma (B-Ly) regarding miRNAs associated with clinicopathological features and outcome. The aim of this study was to evaluate differential miRNA expression in a single-center series of pediatric B-AL/B-Ly. Expression profiles of 800 miRNAs in 33 B-AL/B-Ly samples were evaluated using the NanoString nCounter System. Further validation was performed by qPCR utilizing miRNA-specific TaqMan assays. Significantly expressed miRNAs in B-AL/B-Ly were evaluated in silico to identify predicted targeted cancer-related pathways. Analysis of miRNAs deregulated in B-AL/B-Ly compared to normal control lymphoid tissue (NCLT) identified a consistent set of differentially expressed miRNAs, including miR-494-3p, miR-4286, and miR-19a-3p among the higher expressed miRNAs and miR-150-5p, miR-450b-5p, and miR-342-3p among the lower expressed miRNAs in B-AL/B-Ly compared to NCLT (FC &gt; 1.5, <i>p</i>-adj &lt; 0.05). In silico, the main predicted cancer-related signaling pathways targeted by these miRNAs included the MAPK, PI3K-Akt, JAK-STAT, VEGF, TP53, Fas, TGF-β, and MYC signaling pathways (<i>p</i>-adj &lt; 0.05). B-AL and B-Ly segregated into two major miRNA clusters with sets of significantly overexpressed miRNAs (miR-223-3p, miR-451a, miR-150-5p, miR-144-3p, miR-142-3p, and miR-15a-5p) and lower expressed miRNAs (miR-494-3p, miR-4286, miR-1915-3p, miR-125b-5p, and miR-100-5p) in B-AL compared to B-Ly (FC &gt; 1.5, <i>p</i>-adj &lt; 0.05). Notably, significant downregulation of miR-10a-5p (FC &gt; 1.5, <i>p-</i>adj &lt; 0.05) was observed in the unfavorable outcome group. In summary, new miRNA signatures of relevance in B-AL and B-Ly could be recognized in this study. Studies in larger cohorts are required to further validate these findings.</p>

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miRNA profiling in pediatric and young adult Burkitt leukemia and lymphoma

  • Björn Schneider,
  • Caterina Redwanz,
  • Veronica Celis,
  • Elena Esperanza-Cebollada,
  • Sara Montesdeoca,
  • Itziar Salaverria,
  • Silvia Planas,
  • Nuria Conde,
  • Mireia Camós,
  • Raquel Arnau,
  • Armando Lopez-Guillermo,
  • Claudia Maletzki,
  • Cristina Jou,
  • Andreas Erbersdobler,
  • Olia Shokraie,
  • Almut Meyer-Bahlburg,
  • Manfred Ballmann,
  • Jaume Mora,
  • Elias Campo,
  • Carl Friedrich Classen,
  • Teresa M. Cardesa-Salzmann

摘要

A translational gap exists in Burkitt leukemia (B-AL) and Burkitt lymphoma (B-Ly) regarding miRNAs associated with clinicopathological features and outcome. The aim of this study was to evaluate differential miRNA expression in a single-center series of pediatric B-AL/B-Ly. Expression profiles of 800 miRNAs in 33 B-AL/B-Ly samples were evaluated using the NanoString nCounter System. Further validation was performed by qPCR utilizing miRNA-specific TaqMan assays. Significantly expressed miRNAs in B-AL/B-Ly were evaluated in silico to identify predicted targeted cancer-related pathways. Analysis of miRNAs deregulated in B-AL/B-Ly compared to normal control lymphoid tissue (NCLT) identified a consistent set of differentially expressed miRNAs, including miR-494-3p, miR-4286, and miR-19a-3p among the higher expressed miRNAs and miR-150-5p, miR-450b-5p, and miR-342-3p among the lower expressed miRNAs in B-AL/B-Ly compared to NCLT (FC > 1.5, p-adj < 0.05). In silico, the main predicted cancer-related signaling pathways targeted by these miRNAs included the MAPK, PI3K-Akt, JAK-STAT, VEGF, TP53, Fas, TGF-β, and MYC signaling pathways (p-adj < 0.05). B-AL and B-Ly segregated into two major miRNA clusters with sets of significantly overexpressed miRNAs (miR-223-3p, miR-451a, miR-150-5p, miR-144-3p, miR-142-3p, and miR-15a-5p) and lower expressed miRNAs (miR-494-3p, miR-4286, miR-1915-3p, miR-125b-5p, and miR-100-5p) in B-AL compared to B-Ly (FC > 1.5, p-adj < 0.05). Notably, significant downregulation of miR-10a-5p (FC > 1.5, p-adj < 0.05) was observed in the unfavorable outcome group. In summary, new miRNA signatures of relevance in B-AL and B-Ly could be recognized in this study. Studies in larger cohorts are required to further validate these findings.