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Acute Lymphoblastic Leukemia (ALL) is a rapidly progressive cancer characterized by excessive immature leukocytes, which transform into leukemic cells and proliferate uncontrollably into lymphoblasts, blocking the production of normal cells. T-ALL constitutes 10–15% of pediatric ALL cases. Unlike B-ALL, T-ALL lacks clinically defined molecular subtypes, hindering risk assessment and treatment determination.


In this study, we aimed to identify connections between clinical findings and gene expression in pediatric T-ALL to move towards defining more clinically meaningful subtypes of pediatric T-ALL.


We analyzed clinical and gene expression (bulk and single-cell RNAseq) data from eight pediatric T-ALL patients from the Children’s Mercy Research Institute Biorepository. By utilizing various clinical data types (e.g., flow cytometry, FISH, microarray), we identified clinically relevant mutations and gene expression patterns. This offered further insight into characterizing individual patients and establishing related groups of patients.


Our investigation revealed similarities in gene expression involving LEF1, NOTCH1, and RUNX1 among two patients. In the same patients, we also observed T-cell receptor alpha (TRA) rearrangements with TAL and TLX1, indicating consistency between genomic and transcriptome findings. Furthermore, a patient with ETP-ALL had a high proportion of hematopoietic stem cells (HSC)-like cells, while another patient (not classified with ETP-ALL) displayed similar proportions of HSC-like cells and an elevated expression of genes including IL-7 and LMO2 compared to other patients. Moreover, our analysis identified differential expression of ETV6 and TOX across our cohort, providing potential biomarkers for T-ALL subtyping.


Similarities in gene expression patterns among T-ALL patients, even within our small cohort, emphasize the need for refined classifications of distinct subtypes to improve treatment selection and outcomes. Additionally, we found that a patient without clinically defined ETP-ALL criteria shares a similar molecular profile as the patient with Early T-cell Precursor (ETP)-ALL. Patterns of gene and cell surface marker expression offer potential biomarkers for characterizing T-ALL subtypes and prognosis. Furthermore, the diverse signaling pathway activities identified through bulk and single-cell RNA analyses present potential therapeutic targets for treatment strategies. Future exploration utilizing external gene expression datasets is planned to validate findings within the broader context of Children’s Mercy’s cohort of T-ALL patients and lay the foundation for more personalized approaches to diagnosing and treating pediatric T-ALL.

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Clinical and gene expression data reveal subtypes of pediatric T-cell acute lymphoblastic leukemia