ibs.GRANADA researchers discover a gene associated with the prognosis of childhood leukemia
This finding, published in the Blood Cancer Journal, could help make more accurate diagnoses and predict the risk of relapse in childhood leukemia
The Cancer Genetics, Biomarkers and Experimental Therapies research group at the Granada Biosanitary Research Institute (ibs.GRANADA) has identified that low levels of a gene called TCL6 may be associated with increased survival in childhood leukemia.
Despite scientific advances in recent decades, cancer remains the leading cause of death in the pediatric population. Childhood cancer is a rare disease, with an annual incidence of 144 cases per million children and today with a cure rate of 80%. However, leukemias are the most prevalent childhood neoplasms with approximately 30% of cases, around 350 leukemias are diagnosed each year in our country, and although the cure rates are high, childhood leukemia is still the neoplasm that causes the most deaths causes in those under twenty years of age.
Within childhood leukemia there are several types, acute lymphoblastic leukemia (ALL) being the most frequent in children and characterized by chromosomal alterations such as translocations, amplifications and aneuploidies. These alterations have important implications for the diagnosis, classification and prognosis of the disease, being key in making therapeutic decisions.
Among these alterations is the reciprocal translocation, which is a chromosomal rearrangement, which occurs more frequently in pediatric B-cell acute lymphoblastic leukemia (B-ALL) with an incidence of 25%. This rearrangement, together with an increase in the number of chromosomes, is associated with a favorable prognosis, but up to 20% of pediatric patients with positive B-ALL experience a late relapse of the disease.
Until several years ago, the research carried out on this disease focused only on the protein-coding DNA, which represents only 2% of the genome, and the non-protein-coding RNAs capable of regulating the expression of the rest of the genes were ignored. It is in this line of research, where this team of scientists from Granada has carried out a comparative study in pediatric patients with ALL-B, which analyzes the ways in which one of the types of non-protein coding RNA, the so-called lncRNA, is expressed. In addition, they have compared the target genes of these lncRNAs and have combined these data with clinical information and external data.
This ibs.GRANADA research group has managed to identify 19 lncRNA/target gene pairs that were expressed differently between positive and negative pediatric B-ALL, and between tumor cells and normal cells. Only two pairs, TCL6 and AL133346.1, were consistently correlated across all analyzed datasets. But when studying whether the expression of the TCL6 and AL133346.1 lncRNAs could predict survival, they observed a statistically significant decrease in disease-free survival in patients with "low TCL6" compared to "high TCL6."
This team of researchers has identified TCL6 as a novel lncRNA associated with ETV6-RUNX1-positive pediatric B-ALL, concluding that low levels of TCL6 may be associated with lower disease-free survival. In addition, the analysis of lncRNA expression could contribute to an improvement in the diagnosis of pediatric B-ALL, which allows a better stratification of patients in treatment groups based on the risk of relapse.
These scientists, belonging to the Granada biomedical research institute ibs.GRANADA and the University of Granada, collaborate with the Heroes to the Bone Association and various Spanish hospitals (Hospital La Paz in Madrid, Regional Hospital in Malaga, San Juan de Dios in Barcelona) in the identification of new biomarkers for pediatric ALL. In addition, the Heroes to the Bone Association and the University of Granada have signed a collaboration agreement for the creation of the Research Classroom against childhood leukemia. Research against childhood leukemia and raising awareness about the donation of blood parents as weapons to fight this disease are the main objectives of this Leukemia Heroes Against Leukemia Research Classroom.
About the research group
The main objective of the Cancer Genetics, Biomarkers and Experimental Therapies research group at ibs.GRANADA, led by Dr. Marta Cuadros Celorrio and Pedro Medina Vico, is to identify new biomarkers to improve the diagnosis, prognosis and treatment of patients with Cancer. All this, through the study of new mechanisms of gene regulation, very important for tumor development, such as chromatin remodeling complexes and non-coding RNAs. This group aims to transfer molecular findings to daily clinical practice, using state-of-the-art technologies with patient samples, public repositories of genomic data, cell lines and pre-clinical in vivo models to validate the role of new biomarkers in cancer.
More information about the group at https://www.ibsgranada.es/grupos-de-investigacion/ae22-genetica-del-cancer-biomarcadores-y-terapias-experimentales/
Bibliographic reference:
Cuadros M, Andrades Á, Coira IF, et al. Expression of the long non-coding RNA TCL6 is associated with clinical outcome in pediatric B-cell acute lymphoblastic leukemia. Blood Cancer J. 2019;9(12):93. doi:10.1038/s41408-019-0258-9.
Cuadros M, García DJ, Andrades A, Arenas AM, Coira IF, Baliñas-Gavira C,
Peinado P, Rodríguez MI, Álvarez-Pérez JC, Ruiz-Cabello F, Camós M, Jiménez-Velasco A, Medina PP. LncRNA-mRNA Co-Expression Analysis Identifies AL133346.1/CCN2 as Biomarkers in Pediatric B-Cell Acute Lymphoblastic Leukemia. Cancers (Basel). 2020;17;12(12):3803. doi:10.3390/cancers12123803.