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Background Immunotherapy has emerged as an attractive approach to improve outcomes for pediatric patients with B-ALL or AML. This includes bispecific T-cell engagers and the infusion of genetically modified autologous T cells. In contrast to B-ALL, both T cell-based immunotherapies show limited efficacy for AML. To better understand this difference, we performed a detailed transcriptomic analysis of autologous T cells in pediatric patients with B-ALL and AML taken advantage of publicly accessible single-cell RNA sequencing data.Methods We analyzed 123 samples form three sources: 89 pediatric B-ALL, 25 pediatric AML, and 2 healthy donors (age 25, 26) from ScPCA (https://scpca.alexslemonade.org/); 4 healthy donors (age 18 to 30) from PMID: 32692727 and 3 healthy donors (mean age 2.7) from PMID: 32415257. Most B-ALL and AML samples (107/114) were obtained at diagnosis. All samples were bone marrow, except for 3 B-ALL peripheral blood samples. T cells were clustered and annotated into subtypes using marker genes derived from PMID: 37248301. We compared the proportions of each T cell subtype between B-ALL and AML patients and further investigated associations between T cell subtype composition and clinical characteristics.Results We identified 17 clusters of T cells: 5 CD8, 5 CD4, and 5 CD4+/CD8+ positive, one proliferative cluster and one cluster consisted of gd T cells. Within the CD8+ T cell compartment, three dominant clusters included one naïve-like and one effector cluster. Within the CD4+ T cell compartment, the naïve-like cluster was predominant. Differences appeared in 9 clusters between healthy donors and leukemia samples (the small healthy donor group limited statistical analysis). Comparing B-ALL and AML revealed significant differences in 9 clusters. B-ALL samples had a higher proportion of CD4 T cells than AML samples, mainly due to increased CD4 naïve-like T cells. Additionally, B-ALL samples had a greater abundance of proliferative T cells. Likewise, several rare T cell subtypes also displayed significant differences.Conclusions Our comprehensive analysis revealed significant differences in the T cell compartment of the bone marrow between pediatric B-ALL and AML. In particular, the bone marrow of patients with B-ALL had a higher proportion of CD4 naïve-like and proliferative T cells compared to AML. Our findings offer new insights into the T cell landscape of pediatric leukemia and may inform future strategies to improve T cell-based immunotherapeutics.