Marta Cuadros*, Álvaro Andrades*, Isabel F. Coira, Carlos Baliñas, María I. Rodríguez, Juan Carlos Álvarez-Pérez, Paola Peinado, Alberto M. Arenas, Daniel J. García, Pilar Jiménez, Mireia Camós, Antonio Jiménez-Velasco, Pedro P. Medina. Expression of the long non-coding RNA TCL6 is associated with clinical outcome in pediatric B-cell acute lymphoblastic leukemia. Blood Cancer J. 9, 93 (2019). *Contribución equivalente


Marta Cuadros*, Álvaro Andrades*, Isabel F. Coira, Carlos Baliñas, María I. Rodríguez, Juan Carlos Álvarez-Pérez, Paola Peinado, Alberto M. Arenas, Daniel J. García, Pilar Jiménez, Mireia Camós, Antonio Jiménez-Velasco, Pedro P. Medina


The reciprocal translocation t(12;21)(p13;q22)[ETV6/RUNX1] is the most frequent chromosomal rearrangement in pediatric B-cell acute lymphoblastic leukemia(B-ALL). Long non-coding RNAs (lncRNAs) play important roles in numerous diseases and they represent an emerging layer of cancer biology, but their role in ETV6-RUNX1-positive pediatric B-ALL is largely unknown. In this study, we assessed the expression profiles of lncRNAs and associated protein-coding genes in 42 pediatric B-ALL samples (24 ETV6-RUNX1-positive, 18 ETV6-RUNX1-negative) and 4 bone marrows from healthy donors. We used a microarray platform based on a pathway-focused prediction of functional relationships between lncRNAs and protein-coding genes. We identified 117 lncRNAs and 16 lncRNA/mRNA pairs that were differentially expressed between ETV6-RUNX1-positive and ETV6-RUNX1-negative pediatric B-ALL. The most significant differentially expressed lncRNA/mRNA pair was TCL6/TCL1B and the expression of TCL6 and TCL1B were positively correlated. We validated the TCL6/TCL1B differential expression and correlation results on independent external pediatric B-ALL cohorts. Importantly, pediatric B-ALL patients who expressed low levels of TCL6 showed significantly lower disease-free survival than patients with high levels of TCL6 regardless of the chromosome aberrations. These findings provide one of the first detailed descriptions of lncRNA expression profiles in ETV6-RUNX1-positive pediatric B-ALL


La leucemia linfoblástica aguda de células B (B-ALL) pediátrica se caracteriza por presentar aberraciones cromosómicas. La más frecuente da lugar a la fusión de los genes ETV6 y RUNX1. Nuestro estudio revela que los pacientes ETV6-RUNX1+ expresan niveles elevados del ARN no codificante TCL6, que actúa como biomarcador de un pronóstico más favorable. Estos resultados pueden contribuir a una mejor clasificación de los pacientes de B-ALL pediátrica..


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El grupo “Regulación de la expresión génica y cáncer” (CTS-993) de la Universidad de Granada estudia cómo las células tumorales alteran su expresión génica durante su transformación tumoral con el objetivo de mejorar el diagnóstico, pronóstico y terapia del cáncer. Entre las líneas prioritarias de investigación de nuestro grupo se pretende contribuir a elucidar la implicación de los complejos remodeladores de la cromatina y de los ARN no codificantes en desarrollo tumoral.

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