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.

Integrated transcriptome, proteome and single‐cell sequencing uncover the prognostic and immunological features of colony‐stimulating factor 3 receptor in pan‐cancer

“…Single cell sequencing could be used to identify the gene expression and genetic variation in response to the epigenetic modifications and environmental changes 33 . Meanwhile, single cell sequencing could provide new promising strategies for cancer diagnosis, classification, targeted therapy and prognosis prediction 34–36 . In the present study, the heatmap from CancerSEA showed the different correlation between CSF3R expression and multiple functional states in different cancers, such as DNA repair, invasion, cell cycle and inflammation, etc.…”

Involvement of S100A6/S100A11 in T-Cell Immune Regulatory in HCC Revealed by Single Cell RNA-seq

“… 21 Single-cell sequencing could provide new promising strategies for cancer diagnosis, targeted therapy, and prognosis prediction. 22 – 24 We used scRNA-seq to investigate the role of S100s in the immune microenvironment. By completing the hepatocyte atlas and KEGG analysis of each subpopulation, we found that the T-cell subpopulation was enriched for the RAGE receptor signaling pathway.…”

Increasing Complexity of Molecular Landscapes in Human Hematopoietic Stem and Progenitor Cells during Development and Aging

“…Given its importance in infant AML, murine and human model systems, combined with single-cell omic assays [ 207 , 208 , 209 ], have been developed to examine the effects of the KMT2A/MLLT3 fusion gene on AML development [ 210 ]. These include the recent development of a transplantable human KMT2A/MLLT3 AML xenograft model, using human UCB CD34 + HSPCs and CRISPR/Cas9 genome editing technologies, which also reported that the developmental age and the genetic background of the human CD34+ HSPCs, as well as the microenvironmental niche in surrogate murine models of hematopoiesis influenced AML progression [ 211 ].…”