In a constitutive knock-in mouse model, PAX5::JAK2 rapidly induced aggressive B-ALL without acquisition of other cooperating mutations (63), which unequivocally implicated that PAX5::JAK2 functions as dual hits, which are PAX5 haploinsufficiency and constitutively active kinase activity, to drive leukemogenesis (63). Here, PAX5 is linked to precursor B-cell acute lymphoblastic leukemia.