The potent selection pressure to lose the wild‐type Pax5 allele in these Pax5Jak2/+ B‐ALL cells was dependent on both the Jak2 kinase activity and the DNA‐binding function of Pax5‐Jak2, as no tumors developed in Pax5Jak2‐KD/+ mice, while one third of the Pax5Prd*‐Jak2/+ tumors still contained the wild‐type Pax5 allele. The gene discussed is PAX5; the disease is acute lymphoblastic leukemia.