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Biology subjects

Silverman, L. B.

Publications and source records attributed to Silverman, L. B..

2 recordsLinked to original sources

Altered immune and treatment response gene expression signatures among poverty-exposed children with B-ALL

Children diagnosed with cancer typically receive standardized treatment regimens. Despite highly protocolized care, children living in poverty experience a greater risk of cancer relapse and higher mortality compared to their more affluent peers.1,2 Acute lymphoblastic leukemia (ALL) is the most prevalent childhood cancer, and children with ALL exposed to poverty are more likely to experience early relapse.3 Using single-cell RNA sequencing to analyze leukemic blasts and their microenvironment at diagnosis we found that poverty-exposed patients with standard-risk B-ALL exhibit transcriptional signatures of steroid resistance at time of diagnosis. Additionally, we observe increased expression of inflammatory signatures in myeloid cells and reduced effector signatures in CD8+ T-cells in children with B-ALL living in poverty. Further investigation of the mechanisms underlying these associations may identify opportunities for risk-adapted therapeutic strategies to improve disease outcomes in pediatric ALL.

cancer biology↗

Comparative analysis of plasma and bone marrow nutrient levels in pediatric B-ALL patients

Nutrient availability in the tumor microenvironment is a key determinant of cancer progression and therapeutic response, yet the physiological nutrient environment for most cancers is poorly understood. In this study, we investigated nutrient levels in pediatric B-cell acute lymphoblastic leukemia (B-ALL) patients across different subtypes undergoing chemotherapy, focusing on both bone marrow and circulation. Our analysis revealed distinct differences in nutrient profiles between leukemic and healthy plasma and among B-ALL subtypes, with hyperdiploid B-ALL exhibiting pronounced alterations in arginine and asymmetric dimethylarginine metabolism. Bone marrow and blood plasma exhibited largely similar metabolite profiles, even after chemotherapy, indicating these environments are metabolically comparable. Comparisons with renal cell carcinoma and non-small cell lung cancer highlighted a unique enrichment of tricarboxylic acid cycle intermediates in the circulation of B-ALL patients. These findings provide a comprehensive view of nutrient dynamics in pediatric B-ALL and identify metabolic alterations that could guide biomarker discovery and new therapeutic strategies.

cancer biology↗