Single-Cell Sequencing: Biological Insight and Potential Clinical Implications in Pediatric Leukemia

Abstract

Single-cell sequencing (SCS) provides high-resolution insight into the genomic, epigenomic, and transcriptomic landscape of oncohematological malignancies including pediatric leukemia, the most common type of childhood cancer. Besides broadening our biological understanding of cellular heterogeneity, sub-clonal architecture, and regulatory network of tumor cell populations, SCS can offer clinically relevant, detailed characterization of distinct compartments affected by leukemia and identify therapeutically exploitable vulnerabilities. In this review, we provide an overview of SCS studies focused on the high-resolution genomic and transcriptomic scrutiny of pediatric leukemia. Our aim is to investigate and summarize how different layers of single-cell omics approaches can expectedly support clinical decision making in the future. Although the clinical management of pediatric leukemia underwent a spectacular improvement during the past decades, resistant disease is a major cause of therapy failure. Currently, only a small proportion of childhood leukemia patients benefit from genomics-driven therapy, as 15-20% of them meet the indication criteria of on-label targeted agents, and their overall response rate falls in a relatively wide range (40-85%). The in-depth scrutiny of various cell populations influencing the development, progression, and treatment resistance of different disease subtypes can potentially uncover a wider range of driver mechanisms for innovative therapeutic interventions.

Keywords: cellular heterogeneity; evolutionary trajectory; pediatric leukemia; single-cell sequencing; targeted therapy.

Figure 1

Emergence of anticancer drugs as approved by the United States Food and Drug Administration. Small-molecule targeted agents with acquired label in acute leukemia are specifically indicated. Agents with on-label approval in pediatric leukemia are marked with asterisk (*).

Figure 2

Current niche and estimated efficacy of small-molecule targeted agents in the clinical management of pediatric acute leukemia. (a) Proportion of patients with pediatric acute leukemia who are eligible for targeted drugs with on-label indications in acute leukemia based on genetic features. (b) Estimated proportion of children with acute leukemia who are expected to benefit from the currently available, on-label small-molecule targeted therapies based on average overall response rates.