Investigation of the Altered Transcriptomic Dynamics of Bone Marrow Adipose Tissue Under Exogenous Stimuli in the Context of AML Pathogenesis
Bone marrow is a critical tissue for hematopoietic stem cell regulation, comprising various cell types, including adipose tissue, which actively contributes to hematopoietic biology. The mechanisms underlying the transcriptomic response of bone marrow adipose tissue to xenobiotic stimuli remain poorly understood, particularly its role in leukemia progression. Acute myeloid leukemia (AML) stromal cells differ significantly from healthy bone marrow stroma, with environmental pollutants and xenobiotics playing a crucial role in pathogenesis. This study investigates the transcriptomic alterations in bone marrow adipose-derived mesenchymal stem cells following aryl hydrocarbon receptor (AhR) agonist and antagonist stimulation. Comparative analyses include healthy donors, Fanconi anemia (FA), and AML samples to elucidate their contributions to leukemia development. Overall design: The study examines the transcriptomic dynamics of bone marrow adipose tissue mesenchymal stem cells (BMAT-MSCs) derived from healthy donors (HD), Fanconi anemia (FA) patients, and acute myeloid leukemia (AML) patients using RNA-seq profiling. BMAT-MSCs were subjected to treatments with a untreated control (Control), the AhR antagonist StemRegenin 1 (SR1, 1.5 uM), the AhR agonist 6-Formylindolo(3,2-b)carbazole (FICZ, 100nM), and the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-a, 100ng/mL) for 18 hours. Prior to these treatments, all samples were synchronized using 100 nM dexamethasone (DEX) for 1 hour.