Genomic and Proteomic Analysis of Pediatric Acute Lymphoblastic Leukemia

Abstract

Pediatric acute lymphoblastic leukemia (ALL) is the most common of these diseases that have a known high genomic and proteomic heterogeneity that dictates the disease progression, its recurrence and treatment response. The paper will be based on a multi-omics (genomic and proteomic) approach that will enable a profound analysis of the molecular context of pediatric ALL using publicly available datasets of TARGET and St. Jude PCGP programs. Genomic analysis results have shown recurrent lesions ETV6-RUNX1 fusions, IKZF1 deletions and BCR-ABL1-like rearrangements involving dysregulated JAK/STAT, PI3K/AKT/mTOR, and MAPK pathways. The proteomic profiling of LC-MS/MS detected 682 proteins whose expression changes are related to the evasion of apoptosis, oxidative stress, and metabolic reorganization, particularly the relapsed ones. Integrative proteogenomic analysis and identification of three molecular subtypes with varying clinical outcome was achieved through moderate mRNA protein concordance. Machine learning-based combined omics models have high predictive accuracy of relapse risk and therapeutic response. The findings indicate the functional complement of proteomics to genomics and the potential of proteogenomics to bridge the gap between the risk stratification and guide the individual therapy. The study will enhance the understanding of leukemogenesis and be useful in the area of precision medicine in treating pediatric ALL.