Abstract 2619: Exploring the genomic landscape of pediatric chronic myeloid leukemia stem cells

Abstract Pediatric chronic myeloid leukemia (CML) accounts for 2-9% of leukemias in children. CML in children has been reported to present with a more aggressive clinical manifestation than adult CML, including a higher white blood count and larger spleens. The molecular basis for these clinical differences remains unknown. Therefore, we hypothesize that the molecular pathogenesis of pediatric CML differs from that of adult CML. Furthermore, CML relapse and resistance to tyrosine kinase inhibitors are due to the persistence of CML stem cells. Bulk RNA-seq data with mRNA from bone marrow (BM) CD34+ cells previously demonstrated differential gene expression and uniquely enriched pathways in pediatric CML compared to adult CML stem cells. Our data also showed significant downregulation of Rho pathway-related genes such as ARGHAP27, VAV2, and DLC1, suggesting different molecular pathways in pediatric and adult CML stem cells. To study the clonal heterogeneity and diversity of pediatric CML stem cells, we performed single-cell RNA seq on CD34+ cells from pediatric CML (n=7) and healthy pediatric (n=2) BM samples using the Stem Pro CD34+ system (Miltenyi Biotec, Inc.) and Chromium Next GEM Single Cell 3’ kit from 10X Genomics. Our preliminary data show 13 clusters from CML and healthy CD34+ cells based on gene expression. Overall, CML clusters show a significant downregulation of immune related genes compared to healthy BM clusters. Pathway enrichment analysis shows differential enrichment of immune-related and inflammatory signaling pathways, such as the immune activation and T cell inhibitory pathways in pediatric CML. Our results suggest that immune dysregulation in pediatric CML stem cells contributes to disease pathogenesis. Current work focuses on characterizing 1) the role of immune-related genes in pediatric CML stem cells and their impact on T cell response and 2) cell surface markers of pediatric CML stem cells to identify potential targets for immunotherapy. Citation Format: Ryan S. Sathianathen, Julietta Picco, Hye Na Kim, Minyoung Youn, Ramesh Nair, Nobuko Hijiya, Kathleen M. Sakamoto. Exploring the genomic landscape of pediatric chronic myeloid leukemia stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2619.