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Biology subjects

Bagchi, D. P.

Publications and source records attributed to Bagchi, D. P..

2 recordsLinked to original sources

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↗

Lipolysis of bone marrow adipocytes is required to fuel bone and the marrow niche during energy deficits

To investigate roles for bone marrow adipocyte (BMAd) lipolysis in bone homeostasis, we created a BMAd-specific Cre mouse model in which we knocked out adipose triglyceride lipase (ATGL, Pnpla2). BMAd-Pnpla2-/- mice have impaired BMAd lipolysis, and increased size and number of BMAds at baseline. Although energy from BMAd lipid stores is largely dispensable when mice are fed ad libitum, BMAd lipolysis is necessary to maintain myelopoiesis and bone mass under caloric restriction. BMAd-specific Pnpla2 deficiency compounds the effects of caloric restriction on loss of trabecular bone, likely due to impaired osteoblast expression of collagen genes and reduced osteoid synthesis. RNA sequencing analysis of bone marrow adipose tissue reveals that caloric restriction induces dramatic elevations in extracellular matrix organization and skeletal development genes, and energy from BMAd is required for these adaptations. BMAd-derived energy supply is also required for bone regeneration upon injury, and maintenance of bone mass with cold exposure.

cell biology↗