Transcriptomic study reveals genes and biochemical pathways associated with clinical evolution of patients with childhood acute lymphoblastic leukemia

ABBATE MARÍA MERCEDES; RUIZ MARÍA SOL; RICCHIERI MARÍA CECILIA; GUERÓN GERALDINE; VAZQUEZ ELBA; COTIGNOLA JAVIER

Congreso; Reunión Conjunta SAIC. SAI. AAFE. NANOMED-AR 2021; 2021

SAIC. SAI. AAFE. NANOMED-AR

Acute lymphoblastic leukemia (ALL) is the most incident pediatric cancer. While considerable progress has been made on treatment efficacy and survival rates, about 15-30% of patients relapse and/or die. We aimed to identify gene-expression profiles in childhood ALL that could help better predict disease outcome, response to treatment and therapy-related toxicity. We collected 39 bone marrow samples at time of diagnosis of ALL from 3 hospitals from Argentina. Total RNA was isolated to perform transcriptome analysis (RNAseq). Clinico-pathological characteristics and disease outcome were evaluated and recorded by oncohematologists. We analyzed differential gene expression (DGE) and gene set variation analysis (GSVA) comparing: early response to prednisone, event-free survival, risks group, acute toxicity and minimal residual disease at day 15. We observed that about 30% of dysregulated genes were non-coding RNAs, being long non-coding RNA (lncRNA) the predominant biotype. We identified 6 differentially expressed pathways relevant to ALL biology (p<0.01) and 7 lncRNAs (MIR99AHG, LINC02866, ZNF385D-AS2, LINC02848, MYO18B-AS1, Lnc-PPDPFL-1, Lnc-RIT2-2; padj≤0.05) among ALL risk groups. Because the biological activity of most lncRNAs is still unknown and under the hypothesis that lncRNAs modulate biochemical pathways, we calculated the correlation between significant lncRNA and pathway expressions. We found that MYO18B-AS1 positively correlated with ?inactivation of MAPKK activity? (r=0.4;p=0.02) and LINC02866 negatively correlated with ?CXCR3 chemokine receptor binding? (r=-0.4;p=0.02) and ?transmembrane receptor protein tyrosine phosphatase activity? (r=-0.4;p=0.01). This study identified dysregulated lncRNAs and biochemical pathways that might be relevant in the pathology of childhood ALL.  The analysis of these gene-expression profiles at diagnosis might help improving risk stratification, therapy efficacy and reducing the occurrence of relapse and toxicity.