All these results show that the IL-6 signaling pathway represents a therapeutic vulnerability in Pax5-dependent B-ALL, and that its targeting could be a promising therapy for this disease, which could also be extended to other hematological diseases, taking into account the high frequency of somatic PAX5 losses-of-function in different types of B cell leukemias. Here, IL6 is linked to precursor B-cell acute lymphoblastic leukemia.