Pax5 restoration in a mouse model of B progenitor acute lymphoblastic leukemia

Hypomorphic mutations of PAX5 occur in one third of B-progenitor acute lymphoblastic leukemias (B-ALLs), however their functional consequences remain undefined. Here we employ advanced transgenic RNAi in mice to suppress endogenous Pax5 expression in the hematopoietic compartment in vivo, which co-operates with activated STAT5 to induce B-ALL. In this model, restoring endogenous Pax5 expression in established B-ALL induces transcriptional and immunophenotypic changes reminiscent of normal B cell differentiation, disabling leukemia-initiating capacity and ultimately causing leukemia clearance. Overall design: Comparison of leukemias harvested from triplicate untreated mice versus triplicate Dox-treated (3 days) mice

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Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK