GSE210924
Cell quiescence and reprogramming are distinctive features of pre-leukemic stem cells [RNA-seq CTV]
The leukemic stem cell concept is well established in B-acute lymphoblastic leukemia (B-ALL). However, the question of how a primary oncogene reprograms stem cell-like properties in committed B-cells and leads to a pre-neoplastic population remains unclear. Here, we used the PAX5-ELN oncogenic model to demonstrate a causal link between the differentiation blockade, the self-renewal and the emergence of pre-leukemic stem cells (pre-LSCs). Through multi-parametric immunophenotyping, we show that PAX5-ELN oncoprotein disrupts the differentiation of pre-leukemic cells by enforcing the IL7r/JAK-STAT signaling pathway. This disruption is associated with the induction of rare and quiescent pre-LSCs that sustain the leukemia-initiating activity, as assessed using the H2B-GFP model. Integration of transcriptomic and chromatin accessibility data reveals that those quiescent pre-LSCs lose B-cell identity and reactivate an immature molecular program, reminiscent of human B-ALL chemo-resistant cells. Collectively, our study sheds new lights on the biological mechanisms underlying the cell-of-origin of leukemia. We  performed gene expression profiling analysis using data obtained from RNA-seq of quiescent, slowly prolfierative or highly proliferative B-cells coming from WT or PEtg mice. Overall design: Comparative gene expression profiling analysis of RNA-seq data for B-cell progenitors PEtg quiescent and proliferative and Wt proliferative. CTVhigh = quiescent CTVlow = proliferating