Differential accessibility landscapes in MLL-AF9-driven leukemia stem cells upon inhibiiton of purine metabolism

Targeted metabolomics analysis of bulk leukemia cells and leukemia stem cells (LSCs) derived from the MLL-AF9-driven acute myeloid leukemia (AML) model, and normal granulocyte-monocyte progenitor (GMP) cells and whole bone marrow (WBM) cells from healthy mice, revealed an enhanced purine metabolism in AML LSCs. Inhibiting the purine biosynthetic pathway using mycophenolate mofetil (MMF) promoted myeloid differentiation and induced alterations in the chromatin accessibility landscape. These findings underscore the pivotal role of purine metabolism in regulating LSC activity. To investigate the alterations of chromatin accessibility landscape in MLL-AF9-driven leukemia stem cells (LSCs), control or MMF-treated LSCs were subjected to tagmentation using Tn5. The assay for transposase-accessible chromatin with sequencing (ATAC-Seq) was performed and the obtained sequencing data were analyzed to identify and characterize changes in the chromatin accessibility landscape. Comparative analysis was conducted between MMF-treated and untreated MLL-AF9-driven LSCs to identify differential chromatin accessibility patterns.