@misc{10481/66383,
year = {2020},
month = {12},
url = {http://hdl.handle.net/10481/66383},
abstract = {Simple Summary: Dysregulation of noncoding RNAs has been described in numerous types
of cancers and it has been associated with oncogenic or tumor suppressor activities. However,
the signature of clinically relevant noncoding RNAs in pediatric B-cell acute lymphoblastic leukemia
is still poorly understood. In a search for long non-coding RNAs that characterize pediatric B-cell acute
lymphoblastic leukemia, we found that the long non-coding RNA AL133346.1 and a neighbouring
protein-coding mRNA (CCN2) were significantly over-expressed in leukemia samples compared
to healthy bone marrow. Survival analysis showed that patients with high CCN2 expression had
a significantly better prognosis. These data suggest that AL133346.1/CCN2 could be useful for
discriminating subtypes of leukemia and that CCN2 expression could predict the prognosis of
pediatric patients with B-cell acute lymphoblastic leukemia.
Abstract: Pediatric acute B-cell lymphoblastic leukemia (B-ALL) constitutes a heterogeneous and
aggressive neoplasia in which new targeted therapies are required. Long non-coding RNAs have
recently emerged as promising disease-specific biomarkers for the clinic. Here, we identified pediatric
B-ALL-specific lncRNAs and associated mRNAs by comparing the transcriptomic signatures of
tumoral and non-tumoral samples. We identified 48 lncRNAs that were di erentially expressed
between pediatric B-ALL and healthy bone marrow samples. The most relevant lncRNA/mRNA pair was AL133346.1/CCN2 (previously known as RP11-69I8.3/CTGF), whose expression was positively
correlated and increased in B-ALL samples. Their di erential expression pattern and their strong
correlation were validated in external B-ALL datasets (Therapeutically Applicable Research to
Generate E ective Treatments, Cancer Cell Line Encyclopedia). Survival curve analysis demonstrated
that patients with “high” expression levels of CCN2 had higher overall survival than those with
“low” levels (p = 0.042), and this gene might be an independent prognostic biomarker in pediatric
B-ALL. These findings provide one of the first detailed descriptions of lncRNA expression profiles
in pediatric B-ALL and indicate that these potential biomarkers could help in the classification of
leukemia subtypes and that CCN2 expression could predict the survival outcome of pediatric B-cell
acute lymphoblastic leukemia patients.},
organization = {Aula de Investigación sobre la Leucemia infantil: Héroes contra la Leucemia the Ministry of Economy of Spain 	
SAF2015-67919-R},
organization = {Junta de Andalucía

PIGE-0440-2019
Pl-0245-2017
PI-0135-2020},
organization = {University of Granada 	
PPJIA2019-06
B-CTS-126-UGR18},
organization = {Spanish Association for Cancer Research (LAB-AECC)},
organization = {Spanish Ministry of Education, Culture and Sports FPU fellowship 	
FPU17/00067
FPU17/01258},
organization = {PhD "La Caixa Foundation" fellowship 	
LCF/BQ/DE15/10360019},
organization = {Marie Sklodowska Curie Actions postdoctoral fellowship (H2020-MSCA-IF-2018)},
organization = {"Fundacion Benefica Anticancer Santa Candida y San Francisco Javier" predoctoral fellowship},
publisher = {Mdpi},
keywords = {CTGF},
keywords = {CCN2},
keywords = {AL133346.1},
keywords = {lncRNA expression},
keywords = {Biomarker},
keywords = {Pediatric B-ALL},
title = {LncRNA-mRNA Co-Expression Analysis Identifies AL133346.1/CCN2 as Biomarkers in Pediatric B-Cell Acute Lymphoblastic Leukemia},
doi = {10.3390/cancers12123803},
author = {Cuadros Celorrio, Marta Eugenia and García García, Daniel Jesús and Andrades Delgado, Álvaro and Arenas Molina, Alberto Manuel and Fernández Coira, Isabel and Baliñas Gavira, Carlos and Peinado, Paola and Rodríguez Lara, María Isabel and Álvarez Pérez, Juan Carlos and Ruiz-Cabello Osuna, Francisco and Medina Vico, Pedro Pablo},
}