To study the role of PAX5‐JAK2 (Appendix Fig S1A) in B‐ALL development, we used ES cell targeting to generate a mouse model by inserting human cDNA sequences, starting with exon 4 and encoding the remaining PAX5‐JAK2 protein, into the mouse Pax5 locus to recapitulate the corresponding human rearrangement as closely as possible (Fig 1A and Appendix Fig S1B and C). Here, JAK2 is linked to acute lymphoblastic leukemia.