Herein, we describe how the temporary malfunction of innate immune signaling plays a key role in this process in Pax5+/− mice, and we identify how this is mediated by a molecular mechanism based on the partial downregulation of Myd88, finally leading to B-ALL in Pax5+/− mice. The gene discussed is MYD88; the disease is precursor B-cell acute lymphoblastic leukemia.